N-methylbenzamide

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

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 2:1) 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 2:1) as the eluent.

Conditions: temp:80.01; pressure:0.00; stir:

Procedure: In an argon filled glove box, a 5.0 mL wheaton microreactor was charged with [Ir(cod)(OMe)]2 (1.98 mg, 1.5 mol%), L1 ligand (2.1 mg, 3.5 mol%), B2pin2 (50.8 mg, 1.0 equiv.), KOtBu (1.0 mg, 4.5 mol%) and dry THF (1.0 mL). The reaction mixture was stirred for 2 minutes at room temperature. To this mixture, N-methylbenzamide (27.0 mg, 0.2 mmol) was added. The microreactor was capped with a teflon pressure cap and placed into pre-heated aluminum block at 80 oC. After 12 h (judged by GC/MS, conv: 33%), THF was removed under reduced pressure and chromatographic separation with silica gel (15% ethyl acetate in hexane as eluent) gave the metaborylated product 2b (7.8 mg, 15%) as white solid.

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

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

Procedure: N-Methyl benzamide (55.97 g., 418 mmole) and thionyl chloride (114.7 g, 0.96 mole) were treated as in Example I. Yield 58.4 g (91%) of the title compound, b.p. 80°-90° C. (~0.1 mm Hg).

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

Procedure: (S)-N-[2-(3,4-Dichlorophenyl)-4-[4-[(2,2,2-trifluoroacetyl)-[2-(2,2,2-trifluoroacetylamino)ethyl]amino]piperidino]butyl]-N-methylbenzamide. Using the procedure of Example 1, replacing 4-(2-oxo-1,3-oxazolidin-3-yl)piperidine by 4-[(2,2,2-trifluoroacetyl)-[3-(2,2,2-trifluoroacetylamino)propyl]amino]piperidine, and N-[2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methylbenzamide by the (S)-enantiomer, the N-methylbenzamide was obtained; MS: m/z=683(M+1).

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

Procedure: (S)-N-[2-(3,4-Dichlorophenyl)-4-[4-[(2,2,2-trifluoroacetyl)[2-(2,2,2-trifluoroacetylamino)ethyl]amino]piperidino]-butyl]-N-methylbenzamide. Using the procedure of Example 1, replacing 4-(2-oxo-1,3-oxazolidin-3-yl)piperidine with 4-[(2,2,2-trifluoroacetyl)[2-(2,2,2-trifluoroacetylamino)ethyl]amino]piperidine, and N-[-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methylbenzamide with the (S)-enantiomer, the N-methylbenzamide was obtained as a viscous oil; MS: m/z=669(M+1).

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a flask equipped with a stirrer, dropping funnel, condenser and gas inlet tube maintained under a nitrogen atmosphere there is added at room temperature 19.7 g (0.146 mole) of N-methyl benzamide and 400 ml. dry tetrahydrofuran. The reaction flask is immersed in an ice bath and cooled to an internal temperature of 5°C. Stirring is initiated and 204 ml. of 1.6 M. n-butyl lithium (~0.321 mole) in hexane is added dropwise over about 1 hour maintaining the temperature below 8°C. The resulting dilithio salt is stirred at 5°C. for an additional hour and then a solution of 40 g. (0.146 mole) of 4'-chloro-2-dimethylaminomethyl benzophenone in 500 ml. tetrahydrofuran is added dropwise over about 1 hour maintaining the temperature between -10 to 10°C. The resulting mixture is stirred at 5°C. for 1 hour longer and 150 ml. of saturated ammonium chloride is added maintaining the temperature at about 10°C. The layers are separated and the organic phase dried over ahydrous magnesium sulfate, filtered and evaporated in vacuo. The residue is crystallized from ether to give α-(4-chlorophenyl)-α-(2-dimethylaminomethyl phenyl)-α-hydroxy-N-methyl-o-toluamide; m.p. 154°-156°C. To a flask equipped with a stirrer maintained under a nitrogen atmosphere The reaction flask is immersed in an ice bath maintaining the temperature below 8°C maintaining the temperature between -10 to 10°C The resulting mixture is stirred at 5°C. for 1 hour longer maintaining the temperature at about 10°C The layers are separated the organic phase dried over ahydrous magnesium sulfate filtered evaporated in vacuo The residue is crystallized from ether

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a flask equipped with a stirrer, dropping funnel, condenser and gas inlet tube maintained under a nitrogen atmosphere there is added at room temperature 19.7 g (0.146 mole) of N-methyl benzamide and 400 ml. dry tetrahydrofuran. The reaction flask is immersed in an ice bath and cooled to an internal temperature of 5°C. Stirring is initiated and 204 ml. of 1.6 M. n-butyl lithium (~0.321 mole) in hexane is added dropwise over about 1 hour maintaining the temperature below 8°C. The resulting dilithio salt is stirred at 5°C. for an additional hour and then a solution of 40 g. (0.146 mole) of 4'-chloro-2-dimethylaminomethyl benzophenone in 500 ml. tetrahydrofuran is added dropwise over about 1 hour maintaining the temperature between -10 to 10°C. The resulting mixture is stirred at 5°C. for 1 hour longer and 150 ml. of saturated ammonium chloride is added maintaining the temperature at about 10°C. The layers are separated and the organic phase dried over ahydrous magnesium sulfate, filtered and evaporated in vacuo. The residue is crystallized from ether to give α-(4-chlorophenyl)-α-(2-dimethylaminomethyl phenyl)-α-hydroxy-N-methyl-o-toluamide; m.p. 154°-156°C. To a flask equipped with a stirrer maintained under a nitrogen atmosphere The reaction flask is immersed in an ice bath maintaining the temperature below 8°C maintaining the temperature between -10 to 10°C The resulting mixture is stirred at 5°C. for 1 hour longer maintaining the temperature at about 10°C The layers are separated the organic phase dried over ahydrous magnesium sulfate filtered evaporated in vacuo The residue is crystallized from ether

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

Procedure: To a suspension (10 ml) of sodium hydride (0.24 g, 10 mmoles) in dimethylformamide was added dropwise at 0° C. a dimethylformamide solution (1 ml) of N-methylbenzamide (1.35 g, 10 mmoles). After completion of the addition, the temperature was raised to room temperature, and after stirring for 15 minutes, 3-bromocycloheptene (1.75 g, 10 mmoles) was added dropwise. The resulting mixture was stirred at room temperature for 24 hours, poured into water (20 ml) and extracted with ether. The oily product obtained by concentration was purified by chromatography on silica gel to obtain 0.92 g of N-methyl-N-(2-cycloheptenyl)benzamide [Compound (54)]. After completion of the addition The resulting mixture was stirred at room temperature for 24 hours extracted with ether The oily product obtained by concentration was purified by chromatography on silica gel

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

Procedure: To a suspension (10 ml) of sodium hydride (0.24 g, 10 mmoles) in dimethylformamide was added dropwise at 0° C. a dimethylformamide solution (1 ml) of N-methylbenzamide (1.35 g, 10 mmoles). After completion of the addition, the temperature was raised to room temperature, and after stirring for 15 minutes, 3-bromocycloheptene (1.75 g, 10 mmoles) was added dropwise. The resulting mixture was stirred at room temperature for 24 hours, poured into water (20 ml) and extracted with ether. The oily product obtained by concentration was purified by chromatography on silica gel to obtain 0.92 g of N-methyl-N-(2-cycloheptenyl)benzamide [Compound (54)]. After completion of the addition The resulting mixture was stirred at room temperature for 24 hours extracted with ether The oily product obtained by concentration was purified by chromatography on silica gel