阅读说明：本技术 一种苯并内酰胺类化合物的合成方法 (Synthetic method of benzo lactam compound ) 是由 傅颖 李瑞娟 李明鹏 于 2021-01-12 设计创作，主要内容包括：本发明提供了一种苯并内酰胺类化合物的合成方法,是在乙酸与水的混合溶剂中,以对苯二酚与N-烷基-4-哌啶酮为原料,酞菁铁(II)作为光敏剂,在O_2氛围、白光照射下室温反应12~36 h后纯化而得。本发明将对苯二酚与N-烷基-4-哌啶酮在光催化的条件下,通过交叉脱羟基胺化的方法合成苯并内酰胺类化合物,首次实现了叔胺用于苯酚的胺化,具有反应成本低,合成效率高,合成操作简便,反应条件温和,且具有很高的化学和区域选择性。(The invention provides a method for synthesizing a benzo lactam compound, which comprises the step of dissolving hydroquinone and water in a mixed solvent of acetic acid and water N -alkyl-4-piperidones as starting materials, iron (II) phthalocyanine as photosensitizer, in O 2 Reacting at room temperature for 12-36 h under the irradiation of atmosphere and white light, and purifying to obtain the product. The invention relates to the reaction of hydroquinone with N The benzo lactam compound is synthesized by the cross dehydroxylation amination method of the-alkyl-4-piperidone under the photocatalysis condition, the tertiary amine is used for amination of phenol for the first time, and the method has the advantages of low reaction cost, high synthesis efficiency, simple and convenient synthesis operation, mild reaction condition and high chemical and regioselectivity.)

1. a process for synthesizing the benzolactam compound from hydroquinone in the mixed solvent of acetic acid and waterN-alkyl-4-piperidones as starting materials, iron (II) phthalocyanine as photosensitizer, in O₂Reacting at room temperature for 12-36 h under the irradiation of atmosphere and white light, and purifying to obtain the product.

2. The method for synthesizing a benzo lactam compound according to claim 1, wherein: the structural formula of the hydroquinone is as follows:

R¹is one or more of alkyl and halogen.

3. The method for synthesizing a benzo lactam compound according to claim 1, wherein: the above-mentionedN-alkyl-4-piperidones have the following structural formula:

R²is C₁~C₂₀And one of alkyl, benzyl, allyl, phenylpropyl, propargyl and ester group.

4. The method for synthesizing a benzo lactam compound according to claim 1, wherein: the hydroquinone withNThe molar ratio of the (E) -alkyl-4-piperidone is 1: 1-1: 2.

5. The process for producing a benzo lactam compound according to claim 1, wherein: the dosage of the photosensitizer iron phthalocyanine (II) is 1-3% of the molar weight of p-phenylene diphenols.

6. The process for the photocatalytic synthesis of a compound of the type of a benzamide according to claim 1, wherein: in the mixed solvent, the volume ratio of acetic acid to water is 1: 1-1: 3.

Technical Field

The invention belongs to the technical field of organic synthesis, relates to a synthesis method of a benzo lactam compound, and relates to visible light-promoted hydroquinone andN-alkyl-4-piperidones, a process for the synthesis of benzolactams by dehydroxylation cross-amination.

Background

The benzo lactam compound is widely applied in the fields of natural product chemistry, pharmaceutical research and the like. For example, Benzazepril is an angiotensin converting enzyme inhibitor [ alpha ], [ betaJ. Clin. Invest., 1987, 80, 867-874]. (±) -z-Clausenamide found in leaf of keel of Brassica plant can protect liver and relieve amnesia of humanChin. Chem. Lett., 1991, 2, 291-292]. Alsterpaullone is a cyclin dependent kinase inhibitor [ alpha ], [ alpha ]Eur. J. Biochem., 2000, 267, 5983–5994.]. Therefore, the temperature of the molten metal is controlled,the synthesis of the benzo lactam compound has become one of the hot spots of the research of chemists in recent years. However, because of the intermediate size of these heterocycles in synthetic process across ring interactions with great difficulty. Therefore, relatively few literature reports exist on methods for synthesizing such compounds, e.g., intramolecular carbonylationJ. Am. Chem. Soc., 2005, 127, 14776-14784]Ring-closing metathesis [ alpha ]Med. Chem., 2004, 12, 4375-4385]And cyclization reaction [ 2 ]Org. Lett,2007 , 9, 1387-1390]. Therefore, it is necessary to develop a simple and efficient method for synthesizing the benzo lactam compound.

In recent years, aminophenols are widely present in pharmaceuticals, as well as in natural products. Thus, oxidative amination of phenol [ alpha ], [ alphaAngew. Chem. Int. Ed., 2015, 54, 4102-4104](formation of C-N bond) has received wide attentionJ. Med. Chem., 2013, 56, 4104-4115]. However, since the dissociation energy of the C-N bond in the tertiary alkylamine is highAcc. Chem. Res., 2003, 36, 255-263]It is rarely involved in this transformation. Therefore, most current phenol amination processes are limited to primary and secondary amines.

The structural formula of the benzo lactam compound is as follows:

in the formula R¹Is one or more of alkyl and halogen, R²Is C₁~C₂₀And one of alkyl, benzyl, allyl, phenylpropyl, propargyl and ester group.

Disclosure of Invention

The invention aims to provide a method for synthesizing a benzo lactam compound.

The invention relates to a synthesis method of a benzo lactam compound, which comprises the step of using hydroquinone and water to synthesize a mixed solvent of acetic acid and waterN-alkyl-4-piperidones as starting materials, iron (II) phthalocyanine as photosensitizer, in O₂Reacting at room temperature for 12-36 h under atmosphere and white light irradiation, and purifying to obtain the product, wherein the synthetic route is as follows:

the structural formula of the hydroquinone is as follows:

R¹is one or more of alkyl and halogen.

The above-mentionedN-methyl-4-piperidone has the following structural formula:

R²is C₁~C₂₀Any one of alkyl, benzyl, allyl, phenylpropyl, propargyl, and ester group of (a).

The hydroquinone withNThe molar ratio of the-alkyl-4-piperidones is 1:1 to 1:2 (preferably 1: 1.5).

The dosage of the photosensitizer iron (II) phthalocyanine is 1-3% (preferably 2%) of the molar weight of hydroquinone.

In the mixed solvent, the ratio of acetic acid to water is 1: 1-1: 3 (preferably 1: 2).

The product prepared by the invention is characterized by a spectrum, and the synthesized compound is confirmed to be the target compound.

Compared with the prior art, the synthetic method has the following advantages:

1. the invention relates to the reaction of hydroquinone withNThe-alkyl-4-piperidone is synthesized into the benzo lactam compound by a cross dehydroxylation amination method, the tertiary amine is used for amination of phenol for the first time, and the benzo lactam compound has high chemical and regioselectivity;

2. the reaction is completed under the illumination condition, the synthesis efficiency is high, the reaction condition is mild, the operation is simple and convenient, and the cost is low.

Detailed Description

The synthesis of the present invention is further illustrated by the following specific examples.

Example 1: 8-hydroxy-1-methyl-5, 6-dihydrobenzo [ b ] azocin-2, 4 (1H, 3H) -dione

Hydroquinone (55 mg, 0.5 mmol) was added to a 10 mL reaction tube,N-methyl-4-piperidone (86 mg, 0.75 mmol), photosensitizer iron (II) phthalocyanine (11.4 mg, 2 mmol), acetic acid (1 mL) in water (2 mL) in a mixed solvent. The reaction mixture was allowed to react for 36 hours under an oxygen atmosphere at room temperature under 5W of LED white light. After completion, the reaction mixture was washed with NaHCO₃The aqueous solution was quenched, then ethyl acetate (10 mL) was added to dissolve the reaction, which was washed with water (2X 10 mL) and brine (10 mL) in that order. The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purification by silica gel column chromatography of 8-hydroxy-1-methyl-5, 6-dihydrobenzo [ b ]]Azocine-2, 4 (1H, 3H) -dione 74.5 mg, yield 68%.

The nuclear magnetic data for this compound are as follows:¹H NMR (600 MHz, CDCl₃) δ (ppm): 7.23 (dd, J = 8.9, 2.8 Hz, 1H), 7.08 (d, J = 2.7 Hz, 1H), 6.99 (dd, J = 8.8, 2.3 Hz, 1H), 3.22 (td, J = 9.3, 8.7, 4.9 Hz, 1H), 3.10 – 3.06 (m, 1H), 2.85 – 2.79 (m, 1H), 2.70 (q, J = 8.3 Hz, 1H), 2.50 (s, 3H), 2.38 (ddd, J = 13.6, 8.4, 4.9 Hz, 1H), 2.27 – 2.21 (m, 1H).¹³C NMR (151 MHz, CDCl₃) δ (ppm): 202.1 , 166.3 , 152.0 , 128.2 , 120.2 , 114.1 , 108.0 , 95.5 , 65.0 , 55.7 , 41.9 , 36.5. HRMS (ESI) m/z: Calcd for C₁₂H₁₃NO₃ [M+H]⁺ 220.0968; Found 220.0966.

example 2: 8-hydroxy-1- (3-phenylpropyl) -5, 6-dihydrobenzo [ b ] azo-2, 4 (1H, 3H) -dione

A10 mL reaction tube was charged with a mixed solvent of hydroquinone (55 mg, 0.5 mmol), 1- (3-phenylpropyl) -piperidin-4-one (162.8 mg, 0.75 mmol), iron (II) phthalocyanine as a photosensitizer (11.4 mg, 2 mmol), acetic acid (1 mL) and water (2 mL). The reaction mixture was allowed to react for 36 hours under an oxygen atmosphere at room temperature under 5W of LED white light. After completion, the reaction mixture was washed with NaHCO₃The aqueous solution was quenched, then ethyl acetate (10 mL) was added to dissolve the reaction, which was washed with water (2X 10 mL) and brine (10 mL) in that order. The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purifying by silica gel column chromatography, 8-hydroxy-1- (3-phenylpropyl) -5, 6-dihydrobenzo [ b ]]Azo-2, 4 (1H, 3H) -dione 84.1 mg, yield 52%.

The nuclear magnetic data for this compound are as follows:¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.26 (d, J = 7.2 Hz, 1H), 7.23 (d, J = 7.3 Hz, 1H), 7.21 – 7.18 (m, 1H), 7.15 (d, J = 7.5 Hz, 3H), 7.07 (d, J = 2.8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 1H), 3.21 (td, J = 8.4, 4.7 Hz, 1H), 3.10 (d, J = 10.9 Hz, 1H), 2.75 (d, J = 10.7 Hz, 1H), 2.62 (dt, J = 16.1, 7.6 Hz, 5H), 2.34 (ddd, J = 13.4, 8.4, 4.8 Hz, 1H), 2.20 (dt, J = 14.3, 7.5 Hz, 1H), 1.88 (p, J = 7.7 Hz, 2H).¹³C NMR (151 MHz,CDCl₃) δ (ppm): 202.6, 166.5, 151.8, 141.7, 128.3, 128.3, 128.3, 128.3, 125.9, 125.9, 120.2, 114.2, 108.0, 95.2, 63.4, 55.5, 53.8, 35.9, 33.7, 30.0.HRMS (ESI) m/z: Calcd for C₂₀H₂₁NO₃ [M+H]⁺ 324.1594; Found 324.1592.

example 3: 8-hydroxy-1-isopropyl-5, 6-dihydrobenzo [ b ] azocin-2, 4 (1H, 3H) -dione

Hydroquinone (55 mg, 0.5 mmol) was added to a 10 mL reaction tube,N-isopropyl-4-piperidone (105.8 mg, 0.75 mmol), photosensitizer iron (II) phthalocyanine (11.4 mg, 2 mmol), acetic acid (1 mL) and water (2 mL) as a mixed solvent. The reaction mixture was allowed to react for 36 hours under an oxygen atmosphere at room temperature under 5W of LED white light. After completion, the reaction mixture was washed with NaHCO₃The aqueous solution was quenched, then ethyl acetate (10 mL) was added to dissolve the reaction, which was washed with water (2X 10 mL) and brine (10 mL) in that order. The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purification by silica gel column chromatography of 8-hydroxy-1-isopropyl-5, 6-dihydrobenzo [ b ]]Azocine-2, 4 (1H, 3H) -dione 66.7 mg, yield 54%.

The nuclear magnetic data for this compound are as follows:¹H NMR (600 MHz, CDCl₃) δ (ppm): 7.23 (dd, J = 8.9, 2.8 Hz, 1H), 7.10 (d, J = 2.7 Hz, 1H), 6.97 (d, J = 8.9 Hz, 1H), 3.30 – 3.24 (m, 1H), 3.18 (d, J = 10.8 Hz, 1H), 2.80 (d, J = 10.9 Hz, 1H), 2.68 (td, J = 8.9, 7.3 Hz, 1H), 2.58 (p, J = 6.3 Hz, 1H), 2.34 (ddd, J = 13.6, 8.6, 4.9 Hz, 1H), 2.24 – 2.16 (m, 1H), 1.17 (d, J = 6.3 Hz, 3H), 1.14 (d, J = 6.3 Hz, 3H).¹³C NMR (151 MHz, CDCl₃) δ (ppm): 202.5 , 166.4 , 151.7 , 128.3 , 120.2 , 114.1 , 108.2 , 95.1 , 61.5 , 55.0 , 51.6 , 35.8 , 21.3 , 21.2 .HRMS (ESI) m/ z: Calcd for C₁₄H₁₇NO₃ [M+H]⁺ 248.1281; Found 248.1280.

example 4: 1-cyclopropyl-8-hydroxy-5, 6-dihydrobenzo [ b ] azocin-2, 4 (1H, 3H) -dione

Hydroquinone (55 m) was added to a 10 mL reaction tubeg , 0.5 mmol），N-cyclopropyl-4-piperidone (104.3 mg, 0.75 mmol), photosensitizer iron (II) phthalocyanine (11.4 mg, 2 mmol), acetic acid (1 mL) in water (2 mL) as a mixed solvent. The reaction mixture was allowed to react for 36 hours under an oxygen atmosphere at room temperature under 5W of LED white light. After completion, the reaction mixture was washed with NaHCO₃The aqueous solution was quenched, then ethyl acetate (10 mL) was added to dissolve the reaction, which was washed with water (2X 10 mL) and brine (10 mL) in that order. The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purifying by silica gel column chromatography, 1-cyclopropyl-8-hydroxy-5, 6-dihydrobenzo [ b ]]Azocine-2, 4 (1H, 3H) -dione 67.7 mg, yield 55%.

The nuclear magnetic data for this compound are as follows:¹H NMR (600 MHz, CDCl₃) δ (ppm): 7.20 (dd, J = 8.9, 2.8 Hz, 1H), 7.06 (d, J = 2.8 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H), 3.26 (td, J = 8.7, 5.1 Hz, 1H), 3.15 (d, J = 11.1 Hz, 1H), 2.96 (d, J = 11.0 Hz, 1H), 2.85 (q, J = 8.4 Hz, 1H), 2.34 (ddd, J = 11.5, 8.5, 4.2 Hz, 1H), 2.22 – 2.12 (m, 1H), 1.84 (dt, J = 7.1, 3.1 Hz, 1H), 0.63 – 0.44 (m, 4H).¹³C NMR (151 MHz, CDCl₃) δ (ppm): 166.6 , 151.0 , 135.0 , 127.6 , 120.4 , 114.2 , 108.0 , 95.9 , 63.5 , 53.7 , 36.2 , 35.5 , 5.9 , 5.8 .HRMS (ESI) m/z: Calcd for C₁₄H₁₅NO₃ [M+H]⁺ 246.1125; Found 246.1126.

example 5: 1-allyl-8-hydroxy-5, 6-dihydrobenzo [ b ] azo-2, 4 (1H, 3H) -dione

Hydroquinone (55 mg, 0.5 mmol) was added to a 10 mL reaction tube,N-allyl-4-piperidone (104.4 mg, 0.75 mmol), photosensitizer iron (II) phthalocyanine (11.4 mg, 2 mmol), acetic acid (1 mL) in water (2 mL) as a mixed solvent. In an oxygen atmosphereThe reaction mixture was allowed to react for 36 hours at room temperature under 5W LED white light. After completion, the reaction mixture was washed with NaHCO₃The aqueous solution was quenched, then ethyl acetate (10 mL) was added to dissolve the reaction, which was washed with water (2X 10 mL) and brine (10 mL) in that order. The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purifying by silica gel column chromatography, 1-allyl-8-hydroxy-5, 6-dihydrobenzo [ b ]]Azo-2, 4 (1H, 3H) -dione 53.9 mg, yield 44%.

The nuclear magnetic data for this compound are as follows:¹H NMR (600 MHz, CDCl₃) δ (ppm): 7.21 (dd, J = 8.9, 2.8 Hz, 1H), 7.06 (d, J = 2.8 Hz, 1H), 6.98 (d, J = 8.9 Hz, 1H), 6.00 – 5.89 (m, 1H), 5.26 (dq, J = 17.1, 1.5 Hz, 1H), 5.18 (dd, J = 9.8, 1.3 Hz, 1H), 3.36 – 3.28 (m, 2H), 3.28 – 3.22 (m, 1H), 3.14 (d, J = 11.3 Hz, 1H), 2.86 (d, J = 11.3 Hz, 1H), 2.78 (ddd, J = 9.7, 8.4, 6.9 Hz, 1H), 2.36 (ddd, J= 13.9, 8.4, 5.5 Hz, 1H), 2.22 (dtd, J = 14.0, 7.7, 7.3, 1.2 Hz, 1H), 2.09 (s, 1H).¹³C NMR (151 MHz, CDCl₃) δ (ppm): 201.8 , 166.3 , 151.6 , 133.8 , 127.9 , 120.2 , 118.9 , 114.2 , 108.0 , 94.9 , 62.4 , 58.5 , 53.2 , 35.8 .HRMS (ESI) m/z: Calcd for C₁₄H₁₅NO₃ [M+H]⁺ 246.1125; Found 246.1124.

example 6: 2- (8-hydroxy-2, 4-dioxy-3, 4,5, 6-tetrahydrobenzo [ b ] azo-1 (2H) -yl) acetic acid ethyl ester

A10 mL reaction tube was charged with a mixed solvent of hydroquinone (55 mg, 0.5 mmol), ethyl 2- (4-oxopiperidin-1-yl) acetate (138.8 mg, 0.75 mmol), iron (II) phthalocyanine as a photosensitizer (11.4 mg, 2 mmol), acetic acid (1 mL), and water (2 mL). The reaction mixture was inverted under oxygen atmosphere, room temperature, 5W LED white lamp irradiationIt should be 36 hours. After completion, the reaction mixture was washed with NaHCO₃The aqueous solution was quenched, then ethyl acetate (10 mL) was added to dissolve the reaction, which was washed with water (2X 10 mL) and brine (10 mL) in that order. The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purifying by silica gel column chromatography, 2- (8-hydroxy-2, 4-dioxy-3, 4,5, 6-tetrahydrobenzo [ b ]]Azo-1 (2H) -yl) acetic acid ethyl ester 78.6 mg, yield 54%.

The nuclear magnetic data for this compound are as follows:¹H NMR (400 MHz, CDCl₃) δ (ppm): 7.32 – 7.21 (m, 1H), 7.10 (dd, J = 2.8, 1.3 Hz, 1H), 6.97 (dd, J = 8.9, 1.3 Hz, 1H), 4.32 – 4.02 (m, 2H), 3.49 (dd, J = 8.9, 1.3 Hz, 1H), 3.38 (d, J = 1.3 Hz, 1H), 3.24 (d, J = 10.8 Hz, 1H), 3.04 – 2.77 (m, 2H), 2.53 (s, 1H), 2.44 – 2.27 (m, 1H), 2.22 (dt, J = 13.9, 7.1 Hz, 1H), 1.27 (td, J = 7.0, 1.3 Hz, 3H).¹³C NMR (151 MHz, CDCl₃) δ (ppm): 202.3 , 170.3 , 166.4 , 151.7 , 128.0 , 120.1 , 114.1 , 107.9 , 95.4 , 62.8 , 60.9 , 55.9 , 53.5 , 52.8 , 14.1 .HRMS (ESI) m/ z: Calcd for C₁₅H₁₇NO₅ [M+H]⁺ 292.1179; Found 292.1178.

example 7: 8-hydroxy-1, 9, 10-trimethyl-5, 6-dihydrobenzo [ b ] azo-2, 4 (1H, 3H) -dione

2, 3-Dimethylhydroquinone (69 mg, 0.5 mmol) was added to a 10 mL reaction tube,N-methyl-4-piperidone (86 mg, 0.75 mmol), photosensitizer iron (II) phthalocyanine (11.4 mg, 2 mmol), acetic acid (1 mL) in water (2 mL) in a mixed solvent. The reaction mixture was allowed to react for 36 hours under an oxygen atmosphere at room temperature under 5W of LED white light. After completion, the reaction mixture was washed with NaHCO₃Quenching with aqueous solution, dissolving the reaction system with ethyl acetate (10 mL), and sequentially adding water(2X 10 mL) and brine (10 mL). The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purification by silica gel column chromatography of 8-hydroxy-1, 9, 10-trimethyl-5, 6-dihydrobenzo [ b ]]Azo-2, 4 (1H, 3H) -dione 79.1 mg, yield 64%.

The nuclear magnetic data for this compound are as follows:¹H NMR (600 MHz, CDCl₃) δ (ppm): 6.83 (s, 1H), 3.16 (td, J = 8.6, 4.2 Hz, 1H), 3.00 (d, J = 10.6 Hz, 1H), 2.69 (d, J = 10.6 Hz, 1H), 2.57 (d, J = 8.6 Hz, 1H), 2.45 (s, 3H), 2.33 (ddd, J = 13.8, 8.3, 4.3 Hz, 2H), 2.25 (s, 3H), 2.23 (s, 3H).¹³C NMR (151 MHz, CDCl₃) δ (ppm): 202.7 ,165.9 , 149.7 , 137.0 , 122.8 , 116.6 , 103.9 , 63.6 , 58.1 , 54.2 , 36.1 , 21.8 , 12.0 , 11.3 .HRMS (ESI) m/z: Calcd for C₁₄H₁₇NO₃ [M+H]⁺ 248.1281; Found 248.1279.

example 8: 7, 10-dibromo-8-hydroxy-1-methyl-5, 6-dihydrobenzo [ b ] azo-2, 4 (1H, 3H) -dione

2, 5-dibromohydroquinone (133.95 mg, 0.5 mmol) was added to a 10 mL reaction tube,N-methyl-4-piperidone (86 mg, 0.75 mmol), photosensitizer iron (II) phthalocyanine (11.4 mg, 2 mmol), acetic acid (1 mL) in water (2 mL) in a mixed solvent. The reaction mixture was allowed to react for 36 hours under an oxygen atmosphere at room temperature under 5W of LED white light. After completion, the reaction mixture was washed with NaHCO₃The aqueous solution was quenched, then ethyl acetate (10 mL) was added to dissolve the reaction, which was washed with water (2X 10 mL) and brine (10 mL) in that order. The aqueous phase was further extracted with ethyl acetate (10 mL) and washed as before. The organic phases were combined and washed with anhydrous Na₂SO₄Dried and concentrated. Purification by silica gel column chromatography of 7, 10-dibromo-8-hydroxy-1-methyl-5, 6-dihydrobenzo [ b ]]Azo-2, 4 (1H, 3H) -dione 1312 mg, yield 70%.

The nuclear magnetic data for this compound are as follows:¹H NMR (600 MHz, CDCl₃) δ (ppm): 7.54 (s, 1H), 3.20 – 3.12 (m, 1H), 3.08 (d, J = 11.0 Hz, 1H), 2.79 (d, J = 10.9 Hz, 1H), 2.65 (dt, J = 9.2, 7.8 Hz, 1H), 2.47 (s, 3H), 2.38 (ddd, J = 13.9, 8.1, 4.7 Hz, 1H), 2.33 – 2.25 (m, 1H).¹³C NMR (151 MHz, CDCl₃) δ (ppm): 199.5 , 163.9 , 152.9 , 148.7 , 128.4 , 118.9 , 110.0 , 105.9 , 103.0 , 97.4 , 65.4 , 55.9 , 41.8 , 37.0 .HRMS (ESI) m/z: Calcd for C₁₂H₁₁Br₂NO₃ [M+H]⁺ 375.9178; Found 375.9175.