4-(TRIFLUOROMETHYLTHIO)BENZYL CHLORIDE

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 75 g of sodium cyanide were dissolved in 200 ml of water, and 15 g of tetraethylammonium chloride after 450 g of 4-trifluoromethylmercapto-benzyl chloride were added. The reaction mixture was stirred at 110° C. for 1 hour and then cooled. The cold mixture was diluted with 200 ml of water and then extracted twice with methylene chloride. After drying the organic phase, the solvent was distilled off and the crude product was purified by distillation. 410 g of 4-trifluoromethylmercapto-benzyl cyanide were obtained. Boiling point=95°-97° C./1.5 mm Hg; nD20 =1.5025. cooled extracted twice with methylene chloride After drying the organic phase the solvent was distilled off the crude product was purified by distillation

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 75 g of sodium cyanide were dissolved in 200 ml of water, and 15 g of tetraethylammonium chloride after 450 g of 4-trifluoromethylmercapto-benzyl chloride were added. The reaction mixture was stirred at 110° C. for 1 hour and then cooled. The cold mixture was diluted with 200 ml of water and then extracted twice with methylene chloride. After drying the organic phase, the solvent was distilled off and the crude product was purified by distillation. 410 g of 4-trifluoromethylmercapto-benzyl cyanide were obtained. Boiling point=95°-97° C./1.5 mm Hg; nD20 =1.5025. cooled extracted twice with methylene chloride After drying the organic phase the solvent was distilled off the crude product was purified by distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 700 g of 4-trifluoromethylmercapto-toluene in 2,000 ml of CCl4 were initially introduced into a glass chlorination apparatus and heated to the reflux temperature. The solution was irradiated with a UV lamp. 3 ml of bromine were added before the start of the chlorination. When the color of the bromine had disappeared, 200 g of chlorine were passed in over a period of 6 hours. By fractional distillation over a 40 cm packed column, in addition to non-chlorinated starting material, 560 g of 4-trifluoromethylmercaptobenzyl chloride were obtained. Boiling point=97°-8° C./14 mm Hg, nD20 =1.5072. heated to the reflux temperature The solution was irradiated with a UV lamp were passed in over a period of 6 hours By fractional distillation over a 40 cm in addition

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-[[N-(2-amino-5-chlorobenzoyl)glycyl]aminomethyl]piperidine (16.2 mg, 0.050 mmol) with 4-(trifluoromethylthio)benzyl chloride (20.3 mg, 0.075 mmol), acetonitrile (1.0 mL) and chloroform (0.56 mL) was stirred at 60° C. for 15 hours, cooled, then loaded onto a VarianM SCX column and washed with methanol (15 mL). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated to thereby afford 4-[[N-(2-amino-5-chlorobenzoyl) glycyl]aminomethyl]-1-[4-(trifluoromethylthio)benzyl]piperidine (Compd. No. 1616) (21.9 mg, 85%). The purity was determined by RPLC/MS (96%). ESI/MS m/e 545.2 (M++H, C23H26ClF3N4O2S). cooled washed with methanol (15 mL) The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) concentrated to thereby afford 4-[[N-(2-amino-5-chlorobenzoyl) glycyl]aminomethyl]-1-[4-(trifluoromethylthio)benzyl]piperidine (Compd. No

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-[[N-(2-amino-5-chlorobenzoyl)glycyl]aminomethyl]piperidine (16.2 mg, 0.050 mmol) with 4-(trifluoromethylthio)benzyl chloride (20.3 mg, 0.075 mmol), acetonitrile (1.0 mL) and chloroform (0.56 mL) was stirred at 60° C. for 15 hours, cooled, then loaded onto a VarianM SCX column and washed with methanol (15 mL). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated to thereby afford 4-[[N-(2-amino-5-chlorobenzoyl) glycyl]aminomethyl]-1-[4-(trifluoromethylthio)benzyl]piperidine (Compd. No. 1616) (21.9 mg, 85%). The purity was determined by RPLC/MS (96%). ESI/MS m/e 545.2 (M++H, C23H26ClF3N4O2S). cooled washed with methanol (15 mL) The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) concentrated to thereby afford 4-[[N-(2-amino-5-chlorobenzoyl) glycyl]aminomethyl]-1-[4-(trifluoromethylthio)benzyl]piperidine (Compd. No

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 75 g of sodium cyanide were dissolved in 200 ml of water, and 15 g of tetraethylammonium chloride after 450 g of 4-trifluoromethylmercapto-benzyl chloride were added. The reaction mixture was stirred at 110° C. for 1 hour and then cooled. The cold mixture was diluted with 200 ml of water and then extracted twice with methylene chloride. After drying the organic phase, the solvent was distilled off and the crude product was purified by distillation. 410 g of 4-trifluoromethylmercapto-benzyl cyanide were obtained. Boiling point=95°-97° C./1.5 mm Hg; nD20 =1.5025. cooled extracted twice with methylene chloride After drying the organic phase the solvent was distilled off the crude product was purified by distillation

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 75 g of sodium cyanide were dissolved in 200 ml of water, and 15 g of tetraethylammonium chloride after 450 g of 4-trifluoromethylmercapto-benzyl chloride were added. The reaction mixture was stirred at 110° C. for 1 hour and then cooled. The cold mixture was diluted with 200 ml of water and then extracted twice with methylene chloride. After drying the organic phase, the solvent was distilled off and the crude product was purified by distillation. 410 g of 4-trifluoromethylmercapto-benzyl cyanide were obtained. Boiling point=95°-97° C./1.5 mm Hg; nD20 =1.5025. cooled extracted twice with methylene chloride After drying the organic phase the solvent was distilled off the crude product was purified by distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 700 g of 4-trifluoromethylmercapto-toluene in 2,000 ml of CCl4 were initially introduced into a glass chlorination apparatus and heated to the reflux temperature. The solution was irradiated with a UV lamp. 3 ml of bromine were added before the start of the chlorination. When the color of the bromine had disappeared, 200 g of chlorine were passed in over a period of 6 hours. By fractional distillation over a 40 cm packed column, in addition to non-chlorinated starting material, 560 g of 4-trifluoromethylmercaptobenzyl chloride were obtained. Boiling point=97°-8° C./14 mm Hg, nD20 =1.5072. heated to the reflux temperature The solution was irradiated with a UV lamp were passed in over a period of 6 hours By fractional distillation over a 40 cm in addition

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 700 g of 4-trifluoromethylmercapto-toluene in 2,000 ml of CCl4 were initially introduced into a glass chlorination apparatus and heated to the reflux temperature. The solution was irradiated with a UV lamp. 3 ml of bromine were added before the start of the chlorination. When the color of the bromine had disappeared, 200 g of chlorine were passed in over a period of 6 hours. By fractional distillation over a 40 cm packed column, in addition to non-chlorinated starting material, 560 g of 4-trifluoromethylmercaptobenzyl chloride were obtained. Boiling point=97°-8° C./14 mm Hg, nD20 =1.5072. heated to the reflux temperature The solution was irradiated with a UV lamp were passed in over a period of 6 hours By fractional distillation over a 40 cm in addition

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 75 g of sodium cyanide were dissolved in 200 ml of water, and 15 g of tetraethylammonium chloride after 450 g of 4-trifluoromethylmercapto-benzyl chloride were added. The reaction mixture was stirred at 110° C. for 1 hour and then cooled. The cold mixture was diluted with 200 ml of water and then extracted twice with methylene chloride. After drying the organic phase, the solvent was distilled off and the crude product was purified by distillation. 410 g of 4-trifluoromethylmercapto-benzyl cyanide were obtained. Boiling point=95°-97° C./1.5 mm Hg; nD20 =1.5025. cooled extracted twice with methylene chloride After drying the organic phase the solvent was distilled off the crude product was purified by distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 700 g of 4-trifluoromethylmercapto-toluene in 2,000 ml of CCl4 were initially introduced into a glass chlorination apparatus and heated to the reflux temperature. The solution was irradiated with a UV lamp. 3 ml of bromine were added before the start of the chlorination. When the color of the bromine had disappeared, 200 g of chlorine were passed in over a period of 6 hours. By fractional distillation over a 40 cm packed column, in addition to non-chlorinated starting material, 560 g of 4-trifluoromethylmercaptobenzyl chloride were obtained. Boiling point=97°-8° C./14 mm Hg, nD20 =1.5072. heated to the reflux temperature The solution was irradiated with a UV lamp were passed in over a period of 6 hours By fractional distillation over a 40 cm in addition

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-[[N-(2-amino-5-chlorobenzoyl)glycyl]aminomethyl]piperidine (16.2 mg, 0.050 mmol) with 4-(trifluoromethylthio)benzyl chloride (20.3 mg, 0.075 mmol), acetonitrile (1.0 mL) and chloroform (0.56 mL) was stirred at 60° C. for 15 hours, cooled, then loaded onto a VarianM SCX column and washed with methanol (15 mL). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated to thereby afford 4-[[N-(2-amino-5-chlorobenzoyl) glycyl]aminomethyl]-1-[4-(trifluoromethylthio)benzyl]piperidine (Compd. No. 1616) (21.9 mg, 85%). The purity was determined by RPLC/MS (96%). ESI/MS m/e 545.2 (M++H, C23H26ClF3N4O2S). cooled washed with methanol (15 mL) The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) concentrated to thereby afford 4-[[N-(2-amino-5-chlorobenzoyl) glycyl]aminomethyl]-1-[4-(trifluoromethylthio)benzyl]piperidine (Compd. No