氯雷他定杂质66

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 17.3 parts of 1-(ethoxycarbonyl)-4-hydroxypiperidine, 24.7 parts of bromodiphenylmethane and 7 parts of potassium carbonate is stirred and heated in an oil-bath for 3 hours at 140° C. The reaction mixture is cooled, water is added and the product is extracted with methylbenzene. The extract is washed a few times with water, dried, filtered and evaporated. The oily residue is distilled, yielding ethyl 4-(diphenylmethoxy)-1-piperidinecarboxylate; bp. 150° C. at 0.4 mm. pressure. The reaction mixture is cooled the product is extracted with methylbenzene The extract is washed a few times with water dried filtered evaporated The oily residue is distilled

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 21.5 parts of ethyl 4-hydroxy-1-piperidinecarboxylate, 35.2 parts of bis(4-fluorophenyl)bromomethane and 8.6 parts of potassium carbonate is stirred and heated in an oil-bath at 140° C. for 3 hours. The reaction mixture is allowed to cool to room temperature and water is added. The product is extracted with methylbenzene. The extract is washed successively with water, a diluted hydrochloric acid solution and a sodium bicarbonate solution, dried, filtered and evaporated. The forerun is distilled off (bp. till 143° C. at 0.5-1 mm. pressure), yielding ethyl 4-[bis(4-fluorophenyl)methoxy]-1-piperidinecarboxylate as an oily residue. to cool to room temperature The product is extracted with methylbenzene The extract is washed successively with water a diluted hydrochloric acid solution and a sodium bicarbonate solution, dried filtered evaporated The forerun is distilled off (bp. till 143° C. at 0.5-1 mm. pressure)

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-ethoxycarbonyl-4-hydroxypiperidine (30.3 g) and triethylamine (23 g) were dissolved in ethyl acetate (182 mL) and the obtained mixture was cooled to 3° C. Methanesulfonyl chloride (22.05 g) was added thereto under stirring while taking caution such that the temperature did not exceed 20° C., and the mixture was continuously stirred under ice cooling for 1 hour. The obtained reaction mixture was washed with water (90 mL×3). The organic layer was isolated and concentrated to obtain a target compound as a light yellow oily substance. The yield amount was 43.09 g (98%). did not exceed 20° C. the mixture was continuously stirred under ice cooling for 1 hour The obtained reaction mixture was washed with water (90 mL×3) The organic layer was isolated concentrated to obtain a target compound as a light yellow oily substance

反应条件: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-ethoxycarbonyl-4-hydroxypiperidine (30.3 g) and triethylamine (23 g) were dissolved in ethyl acetate (182 mL) and the obtained mixture was cooled to 3° C. Methanesulfonyl chloride (22.05 g) was added thereto under stirring while taking caution such that the temperature did not exceed 20° C., and the mixture was continuously stirred under ice cooling for 1 hour. The obtained reaction mixture was washed with water (90 mL×3). The organic layer was isolated and concentrated to obtain a target compound as a light yellow oily substance. The yield amount was 43.09 g (98%). did not exceed 20° C. the mixture was continuously stirred under ice cooling for 1 hour The obtained reaction mixture was washed with water (90 mL×3) The organic layer was isolated concentrated to obtain a target compound as a light yellow oily substance

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 17.3 parts of 1-(ethoxycarbonyl)-4-hydroxypiperidine, 24.7 parts of bromodiphenylmethane and 7 parts of potassium carbonate is stirred and heated in an oil-bath for 3 hours at 140° C. The reaction mixture is cooled, water is added and the product is extracted with methylbenzene. The extract is washed a few times with water, dried, filtered and evaporated. The oily residue is distilled, yielding ethyl 4-(diphenylmethoxy)-1-piperidinecarboxylate; bp. 150° C. at 0.4 mm. pressure. The reaction mixture is cooled the product is extracted with methylbenzene The extract is washed a few times with water dried filtered evaporated The oily residue is distilled

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 21.5 parts of ethyl 4-hydroxy-1-piperidinecarboxylate, 35.2 parts of bis(4-fluorophenyl)bromomethane and 8.6 parts of potassium carbonate is stirred and heated in an oil-bath at 140° C. for 3 hours. The reaction mixture is allowed to cool to room temperature and water is added. The product is extracted with methylbenzene. The extract is washed successively with water, a diluted hydrochloric acid solution and a sodium bicarbonate solution, dried, filtered and evaporated. The forerun is distilled off (bp. till 143° C. at 0.5-1 mm. pressure), yielding ethyl 4-[bis(4-fluorophenyl)methoxy]-1-piperidinecarboxylate as an oily residue. to cool to room temperature The product is extracted with methylbenzene The extract is washed successively with water a diluted hydrochloric acid solution and a sodium bicarbonate solution, dried filtered evaporated The forerun is distilled off (bp. till 143° C. at 0.5-1 mm. pressure)

反应条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 21.5 parts of ethyl 4-hydroxy-1-piperidinecarboxylate, 35.2 parts of bis(4-fluorophenyl)bromomethane and 8.6 parts of potassium carbonate is stirred and heated in an oil-bath at 140° C. for 3 hours. The reaction mixture is allowed to cool to room temperature and water is added. The product is extracted with methylbenzene. The extract is washed successively with water, a diluted hydrochloric acid solution and a sodium bicarbonate solution, dried, filtered and evaporated. The forerun is distilled off (bp. till 143° C. at 0.5-1 mm. pressure), yielding ethyl 4-[bis(4-fluorophenyl)methoxy]-1-piperidinecarboxylate as an oily residue. to cool to room temperature The product is extracted with methylbenzene The extract is washed successively with water a diluted hydrochloric acid solution and a sodium bicarbonate solution, dried filtered evaporated The forerun is distilled off (bp. till 143° C. at 0.5-1 mm. pressure)

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred mixture of 3.5 parts of ethyl 4-hydroxy-1-piperidinecarboxylate and 135 parts of N,N-dimethylformamide was added 1 part of a sodium hydride dispersion 50% and stirring was continued for 2 hours at room temperature. After the addition of 5.2 parts of 2-chloro-1-[(4-fluorophenyl)methyl]-1H-benzimidazole, the whole was further stirred overnight at room temperature. The reaction mixture was poured into ice water and the product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was crystallized from 2,2'-oxybispropane, yielding 2.5 parts (31.5%) of ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]oxy]-1-piperidinecarboxylate; mp. 94.0° C. (26). the whole was further stirred overnight at room temperature the product was extracted with trichloromethane The extract was dried filtered evaporated The residue was crystallized from 2,2'-oxybispropane