反应详情

To a cooled (0° C.) mixture of (S)-3-(cyanodiphenylmethyl)-1-[2-(2,3-dihydrobenzofuran-5-yl)acetyl]pyrrolidine (IV) as a toluene solution (7.43 Kg active, 17.59 moles) and sodium borohydride (0.87 Kg, 23 moles) in tetrahydrofuran (29.7 L) is added boron trifluoride tetrahydrofuran complex (4.31 Kg, 30.81 moles) at such a rate as to maintain the temperature of the reaction below 10° C. The reaction is warmed to ambient temperature and stirred for a further 4 hours. Aqueous piperazine solution is added and the mixture is heated at reflux for 8 hours. The aqueous layer is separated and washed with 1% aqueous sodium chloride solution (22.3 L) at 40° C. The organic layer is concentrated and essentially replaced by isopropyl alcohol at atmospheric pressure to a total volume of about 30 L. The product crystallises on cooling and is collected at 0-5° C. by filtration. (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetonitrile (V) is washed with chilled isopropyl alcohol and dried under vacuum at 50° C. Yield 6.34 Kg (88%).

1. temperatureTo a cooled
2. temperatureto maintain
3. customthe temperature of the reaction below 10° C
4. temperaturethe mixture is heated
5. temperatureat reflux for 8 hours
6. customThe aqueous layer is separated
7. washwashed with 1% aqueous sodium chloride solution (22.3 L) at 40° C
8. concentrationThe organic layer is concentrated
9. customThe product crystallises
10. temperatureon cooling
11. filtrationis collected at 0-5° C. by filtration
12. wash(S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-pyrrolidinyl}-2,2-diphenylacetonitrile (V) is washed with chilled isopropyl alcohol
13. customdried under vacuum at 50° C