1-(2-bromo-4-chlorophenyl)ethanone

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Solid NaBH4 (354 mg, 9.4 mmol) was added to a 0° C., THF (5 mL) and MeOH (15 mL) solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.8 g, 7.8 mmol). After 30 min 2N aqueous HCl was slowly added, and the resulting mixture was extracted with EtOAc. The combined organic extracts were dried (Na2SO4), concentrated, and purified via column chromatography to yield the title compound. the resulting mixture was extracted with EtOAc The combined organic extracts were dried (Na2SO4) concentrated purified via column chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.0 g, 4.28 mmol), tributylamine (2.041 mL, 8.57 mmol), and tert-butyl acrylate (1.255 mL, 8.57 mmol) in DMF (10 mL) was added palladium on carbon (0.456 g, 0.428 mmol) and palladium (II) acetate (0.096 g, 0.428 mmol). The reaction mixture was warmed to 100° C. After 16 h, the reaction was cooled to rt and filtered. The solid was rinsed with DMF and the filtrate was diluted with EtOAc and washed with H2O (2×) followed by brine. The crude product was then dried over Na2SO4, filtered and concentrated. Purification by normal phase chromatography afforded Intermediate 4A (0.760 g, 63%), as a brown oil. MS (ESI) m/z: 225.0 (M-C4H8+H)+. the reaction was cooled to rt filtered The solid was rinsed with DMF the filtrate was diluted with EtOAc washed with H2O (2×) The crude product was then dried over Na2SO4 filtered concentrated Purification by normal phase chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.0 g, 4.28 mmol), tributylamine (2.041 mL, 8.57 mmol), and tert-butyl acrylate (1.255 mL, 8.57 mmol) in DMF (10 mL) was added palladium on carbon (0.456 g, 0.428 mmol) and palladium (II) acetate (0.096 g, 0.428 mmol). The reaction mixture was warmed to 100° C. After 16 h, the reaction was cooled to rt and filtered. The solid was rinsed with DMF and the filtrate was diluted with EtOAc and washed with H2O (2×) followed by brine. The crude product was then dried over Na2SO4, filtered and concentrated. Purification by normal phase chromatography afforded Intermediate 4A (0.760 g, 63%), as a brown oil. MS (ESI) m/z: 225.0 (M-C4H8+H)+. the reaction was cooled to rt filtered The solid was rinsed with DMF the filtrate was diluted with EtOAc washed with H2O (2×) The crude product was then dried over Na2SO4 filtered concentrated Purification by normal phase chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.0 g, 4.28 mmol), tributylamine (2.041 mL, 8.57 mmol), and tert-butyl acrylate (1.255 mL, 8.57 mmol) in DMF (10 mL) was added palladium on carbon (0.456 g, 0.428 mmol) and Pd(OAc)2 (0.096 g, 0.428 mmol). The reaction mixture was warmed to 100° C. After 16 h, the reaction was cooled to rt. The reaction was filtered and the solid was rinsed with DMF. The filtrate was diluted with EtOAc, washed with H2O (2×), brine, dried over Na2SO4, filtered and concentrated. Purification by normal phase chromatography afforded Intermediate 4A (0.760 g, 63%), as a brown oil. MS (ESI) m/z: 225.0 (M-C4H8+H)+. the reaction was cooled to rt The reaction was filtered the solid was rinsed with DMF The filtrate was diluted with EtOAc washed with H2O (2×), brine dried over Na2SO4 filtered concentrated Purification by normal phase chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Solid NaBH4 (354 mg, 9.4 mmol) was added to a 0° C., THF (5 mL) and MeOH (15 mL) solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.8 g, 7.8 mmol). After 30 min 2N aqueous HCl was slowly added, and the resulting mixture was extracted with EtOAc. The combined organic extracts were dried (Na2SO4), concentrated, and purified via column chromatography to yield the title compound. the resulting mixture was extracted with EtOAc The combined organic extracts were dried (Na2SO4) concentrated purified via column chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Solid NaBH4 (354 mg, 9.4 mmol) was added to a 0° C., THF (5 mL) and MeOH (15 mL) solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.8 g, 7.8 mmol). After 30 min 2N aqueous HCl was slowly added, and the resulting mixture was extracted with EtOAc. The combined organic extracts were dried (Na2SO4), concentrated, and purified via column chromatography to yield the title compound. the resulting mixture was extracted with EtOAc The combined organic extracts were dried (Na2SO4) concentrated purified via column chromatography

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (4° C.) and stirred solution of 2-bromo-4-chloroacetophenone (5.0 g, 21.41 mmol) and glacial acetic acid (2.8 mL, 49.25 mmol) in acetonitrile was added triethylamine (6.1 mL, 44.97 mmol). The reaction mixture was warmed to room temperature, than refluxed for 3 hours. The reaction mixture was extracted with ether, acetate, washed with 1N hydrochloric acid, brine, dried, and concentrated to yield 4.1 g of acetic acid 2-(4-chlorophenyl)-2-oxo-ethyl ester. The reaction mixture was warmed to room temperature than refluxed for 3 hours The reaction mixture was extracted with ether, acetate washed with 1N hydrochloric acid, brine dried concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Solid NaBH4 (354 mg, 9.4 mmol) was added to a 0° C., THF (5 mL) and MeOH (15 mL) solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.8 g, 7.8 mmol). After 30 min 2N aqueous HCl was slowly added, and the resulting mixture was extracted with EtOAc. The combined organic extracts were dried (Na2SO4), concentrated, and purified via column chromatography to yield the title compound. the resulting mixture was extracted with EtOAc The combined organic extracts were dried (Na2SO4) concentrated purified via column chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.0 g, 4.28 mmol), tributylamine (2.041 mL, 8.57 mmol), and tert-butyl acrylate (1.255 mL, 8.57 mmol) in DMF (10 mL) was added palladium on carbon (0.456 g, 0.428 mmol) and Pd(OAc)2 (0.096 g, 0.428 mmol). The reaction mixture was warmed to 100° C. After 16 h, the reaction was cooled to rt. The reaction was filtered and the solid was rinsed with DMF. The filtrate was diluted with EtOAc, washed with H2O (2×), brine, dried over Na2SO4, filtered and concentrated. Purification by normal phase chromatography afforded Intermediate 4A (0.760 g, 63%), as a brown oil. MS (ESI) m/z: 225.0 (M-C4H8+H)+. Intermediate 4: A solution of Intermediate 4A (0.048 g, 0.171 mmol) in 50% TFA/DCM (2 mL) was stirred at rt. After 1 h, the reaction was concentrated to give Intermediate 4 (0.038 g, 100% yield) as a yellow solid. The material was carried onto the next step without further purification. MS (ESI) m/z: 225.1 (M+H)+. the reaction was cooled to rt The reaction was filtered the solid was rinsed with DMF The filtrate was diluted with EtOAc washed with H2O (2×), brine dried over Na2SO4 filtered concentrated Purification by normal phase chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.0 g, 4.28 mmol), tributylamine (2.041 mL, 8.57 mmol), and tert-butyl acrylate (1.255 mL, 8.57 mmol) in DMF (10 mL) was added palladium on carbon (0.456 g, 0.428 mmol) and palladium (II) acetate (0.096 g, 0.428 mmol). The reaction mixture was warmed to 100° C. After 16 h, the reaction was cooled to rt and filtered. The solid was rinsed with DMF and the filtrate was diluted with EtOAc and washed with H2O (2×) followed by brine. The crude product was then dried over Na2SO4, filtered and concentrated. Purification by normal phase chromatography afforded Intermediate 4A (0.760 g, 63%), as a brown oil. MS (ESI) m/z: 225.0 (M-C4H8+H)+. the reaction was cooled to rt filtered The solid was rinsed with DMF the filtrate was diluted with EtOAc washed with H2O (2×) The crude product was then dried over Na2SO4 filtered concentrated Purification by normal phase chromatography

Conditions: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (4° C.) and stirred solution of 2-bromo-4-chloroacetophenone (5.0 g, 21.41 mmol) and glacial acetic acid (2.8 mL, 49.25 mmol) in acetonitrile was added triethylamine (6.1 mL, 44.97 mmol). The reaction mixture was warmed to room temperature, than refluxed for 3 hours. The reaction mixture was extracted with ether, acetate, washed with 1N hydrochloric acid, brine, dried, and concentrated to yield 4.1 g of acetic acid 2-(4-chlorophenyl)-2-oxo-ethyl ester. The reaction mixture was warmed to room temperature than refluxed for 3 hours The reaction mixture was extracted with ether, acetate washed with 1N hydrochloric acid, brine dried concentrated

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a degassed solution of 1-(2-bromo-4-chlorophenyl)ethanone (1.0 g, 4.28 mmol), tributylamine (2.041 mL, 8.57 mmol), and tert-butyl acrylate (1.255 mL, 8.57 mmol) in DMF (10 mL) was added palladium on carbon (0.456 g, 0.428 mmol) and palladium (II) acetate (0.096 g, 0.428 mmol). The reaction mixture was warmed to 100° C. After 16 h, the reaction was cooled to rt and filtered. The solid was rinsed with DMF and the filtrate was diluted with EtOAc and washed with H2O (2×) followed by brine. The crude product was then dried over Na2SO4, filtered and concentrated. Purification by normal phase chromatography afforded Intermediate 4A (0.760 g, 63%), as a brown oil. MS (ESI) m/z: 225.0 (M-C4H8+H)+. the reaction was cooled to rt filtered The solid was rinsed with DMF the filtrate was diluted with EtOAc washed with H2O (2×) The crude product was then dried over Na2SO4 filtered concentrated Purification by normal phase chromatography