反应详情

A mixture of 14.3 g of 4,4-bis(p-fluorophenyl)cyclohexanone, 14 g of 4-(4-chloro-3-trifluoromethylphenyl)-4-piperidinol, 0.5 g of p-toluenesulfonic acid and 100 ml of toluene is stirred under reflux for 145 hours, water formed being removed as an azeotropic mixture with toluene. The toluene is then removed, and the residual oil is dissolved in 100 ml of 90% methanol. To the solution is added slowly 19 g of sodium borohydride under cooling. After the addition is complete, the methanol is removed under reduced pressure, water is added to the residue, and the aqueous mixture is extracted with chloroform. The extract is washed with water and dried over sodium sulfate. The residual oil is purified by column chromatography on silica gel using a mixture of chloroform and methanol (9:1) as an eluent. The objective base thus obtained is converted in a conventional manner into the hydrochloride. Thus is obtained 1-[4,4-bis(p-fluorophenyl)cyclohexyl]-4-(4-chloro-3-trifluoromethylphenyl)-4-piperidinol hydrochloride as colorless crystals, melting at 274°-277° C.

1. temperatureunder reflux for 145 hours
2. custombeing removed as an azeotropic mixture with toluene
3. customThe toluene is then removed
4. dissolutionthe residual oil is dissolved in 100 ml of 90% methanol
5. additionTo the solution is added slowly 19 g of sodium borohydride
6. temperatureunder cooling
7. additionAfter the addition
8. customthe methanol is removed under reduced pressure, water
9. additionis added to the residue
10. extractionthe aqueous mixture is extracted with chloroform
11. washThe extract is washed with water
12. dry with materialdried over sodium sulfate
13. customThe residual oil is purified by column chromatography on silica gel using
14. additiona mixture of chloroform and methanol (9:1) as an eluent
15. customThe objective base thus obtained