4-chloro-N-methylbenzamide

Conditions: temp:60.01; pressure:0.00; stir:

Procedure: Isolated by chromatography using deactivated silica gel and ethyl acetate and petroleum ether (10:1 to 1:1) as the eluent.

Conditions: temp:60.01; pressure:0.00; stir:

Procedure: Isolated by chromatography using deactivated silica gel and ethyl acetate and petroleum ether (10:1 to 1:1) as the eluent.

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

Procedure: N-Methyl 4-chlorobenzamide (42.6 g, 251 mmole) and thionyl chloride (153.3 g, 1.28 mole) were reacted as in Example I to yield 39.3 g (83.4%) of the title compound, b.p. 125° C. (15 mm Hg).

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-N-methyl-benzamide (3.1 g) in THF (30 mL) was added n-butyl lithium (30.1 mL of 2.5M hexane solution) and the solution refluxed for 45 min. The solution was then cooled to 0° C. and N-methylformanilide (9.27 mL) added dropwise over 2 min. The solution was then refluxed for 2 h, then cooled to ambient temperature, water (80 mL) added and the solution acidified to pH 1 with 2M HCl. The solution was then extracted three times with ethyl acetate (3×50 mL), washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resulting brown oil was purified on silica by flash chromatography to afford the sub-titled product as a pale yellow solid (2.13 g; 59%). 1H NMR (400 MHz, CDCl3) δ 2.90 (3H, s), 4.25 (1H, d, J) 5.60 (1H, d, J), 7.35 (2H, s), 7.60 (1H, s) ppm. the solution refluxed for 45 min The solution was then refluxed for 2 h cooled to ambient temperature The solution was then extracted three times with ethyl acetate (3×50 mL) washed with brine (20 mL) dried (MgSO4) concentrated in vacuo The resulting brown oil was purified on silica by flash chromatography

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

Procedure: To a 0° C. solution of the 4-chlorobenzoyl chloride (4.50 g) in dichloromethane (10 mL) was added an 8M solution of methylamine in ethanol dropwise. The solution was stirred for 16 h and then evaporated to dryness. The residue was diluted with saturated sodium bicarbonate solution (10 mL) and extracted three times with ethyl acetate (3×20 mL), the organics washed with brine (10 mL), dried (MgSO4) and concentrated in vacuo to afford the sub-title compound as a white solid (4.33 g; 97%). 1H NMR (400 MHz, CDCl3) δ 3.00 (3H, s), 7.40 (1H, br) 7.40 (1H, d), 7.70 (1H, d) ppm. evaporated to dryness The residue was diluted with saturated sodium bicarbonate solution (10 mL) extracted three times with ethyl acetate (3×20 mL) the organics washed with brine (10 mL) dried (MgSO4) concentrated in vacuo

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

Procedure: The starting material is prepared as follows: To a mixture of 1250 ml of a 40% aqueous solution of methylamine and 1250 ml of methylene chloride, cooled in an ice bath, is added with stirring a solution of 500 g of 4-chlorobenzoyl chloride in 625 ml of methylene chloride. After the addition (50 minutes), the mixture is stirred for an additional 2 hours. The white precipitate is filtered off and air dried and the methylene chloride layer of the filtrate is dried and evaporated to give the crude 4-chloro-N-methyl-benzamide, which, after crystallization from 1200 ml of methanol, melts at 158°-161°; an additional amount of the product is recovered from the mother liquor, m.p. 158°-160°. The starting material is prepared cooled in an ice bath is added After the addition (50 minutes) The white precipitate is filtered off air dried the methylene chloride layer of the filtrate is dried evaporated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-N-methyl-benzamide (3.1 g) in THF (30 mL) was added n-butyl lithium (30.1 mL of 2.5M hexane solution) and the solution refluxed for 45 min. The solution was then cooled to 0° C. and N-methylformanilide (9.27 mL) added dropwise over 2 min. The solution was then refluxed for 2 h and then cooled to ambient temperature, water (80 mL) added and the solution acidified to pH 1 with 2M HCl. The solution was then extracted three times with ethyl acetate (3×50 mL), washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resulting brown oil was purified on silica by flash chromatography to afford the sub-titled product as a pale yellow solid (2.13 g; 59%); 1H NMR (400 MHz, CDC13) δ 2.90 (3H, s), 4.25 (1H, d) 5.60 (1H, d), 7.35 (2H, s), 7.60 (1H, s). the solution refluxed for 45 min The solution was then refluxed for 2 h cooled to ambient temperature The solution was then extracted three times with ethyl acetate (3×50 mL) washed with brine (20 mL) dried (MgSO4) concentrated in vacuo The resulting brown oil was purified on silica by flash chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-N-methyl-benzamide (3.1 g) in THF (30 mL) was added n-butyl lithium (30.1 mL of 2.5M hexane solution) and the solution refluxed for 45 min. The solution was then cooled to 0° C. and N-methylformanilide (9.27 mL) added dropwise over 2 min. The solution was then refluxed for 2 h and then cooled to ambient temperature, water (80 mL) added and the solution acidified to pH 1 with 2M HCl. The solution was then extracted three times with ethyl acetate (3×50 mL), washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The resulting brown oil was purified on silica by flash chromatography to afford the sub-titled product as a pale yellow solid (2.13 g; 59%); 1H NMR (400 MHz, CDC13) δ 2.90 (3H, s), 4.25 (1H, d) 5.60 (1H, d), 7.35 (2H, s), 7.60 (1H, s). the solution refluxed for 45 min The solution was then refluxed for 2 h cooled to ambient temperature The solution was then extracted three times with ethyl acetate (3×50 mL) washed with brine (20 mL) dried (MgSO4) concentrated in vacuo The resulting brown oil was purified on silica by flash chromatography

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

Procedure: To a 0° C. solution of the 4-chlorobenzoyl chloride (4.50 g) in dichloromethane (10 mL) was added an 8M solution of methylamine in ethanol dropwise. The solution was stirred for 16 h and then evaporated to dryness. The residue was diluted with saturated sodium bicarbonate solution (10 mL) and extracted three times with ethyl acetate (3×20 mL), the organics washed with brine (10 mL), dried (MgSO4) and concentrated in vacuo to afford the sub-title compound as a white solid (4.33 g; 97%): 1H NMR (400 MHz, CDCl3) δ 3.00 (3H, s), 7.40 (1H, brs) 7.40 (1H, d), 7.70 (1H, d). evaporated to dryness The residue was diluted with saturated sodium bicarbonate solution (10 mL) extracted three times with ethyl acetate (3×20 mL) the organics washed with brine (10 mL) dried (MgSO4) concentrated in vacuo

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

Procedure: N-Methyl 4-chlorobenzamide (42.6 g, 251 mmole) and thionyl chloride (153.3 g, 1.28 mole) were reacted as in Example I to yield 39.3 g (83.4%) of the title compound, b.p. 125° C. (15 mm Hg).

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

Procedure: The starting material is prepared as follows: To a mixture of 1250 ml of a 40% aqueous solution of methylamine and 1250 ml of methylene chloride, cooled in an ice bath, is added with stirring a solution of 500 g of 4-chlorobenzoylchloride in 625 ml of methylene chloride. After the addition (50 minutes), the mixture is stirred for an additional 2 hour. The white precipitate is filtered off and air dried and the methylene chloride layer of the filtrate is dried and evaporated to give the crude 4-chloro-N-methyl-benzamide, which, after crystallization from 1200 ml of methanol melts at 158°-161°; an additional amount of the product is recovered from the mother liquor, m.p. 158°-160°. The starting material is prepared cooled in an ice bath is added After the addition (50 minutes) The white precipitate is filtered off air dried the methylene chloride layer of the filtrate is dried evaporated

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

Procedure: The starting material is prepared as follows: To a mixture of 1250 ml of a 40% aqueous solution of methylamine and 1250 ml of methylene chloride, cooled in an ice bath, is added with stirring a solution of 500 g of 4-chlorobenzoyl chloride in 625 ml of methylene chloride. After the addition (50 minutes), the mixture is stirred for an additional 2 hours. The white precipitate is filtered off and air dried and the methylene chloride layer of the filtrate is dried and evaporated to give the crude 4-chloro-N-methyl-benzamide, which, after crystallization from 1200 ml of methanol, melts at 158°-161°; an additional amount of the product is recovered from the mother liquor, m.p. 158°-160°. The starting material is prepared cooled in an ice bath is added After the addition (50 minutes) The white precipitate is filtered off air dried the methylene chloride layer of the filtrate is dried evaporated