反应详情

温度

10 °C

A solution of 7.0 g of potassium t-butoxide (62.5 mmole) in 20 ml of dry DMF was added dropwise to a chilled solution of 10 g of 1-acetyl-4-ethynyl-4-hydroxypiperidine (59.9 mmole) in 75 ml of dry DMF, at such a rate as to maintain the temperature at 10° C. The mixture was allowed to equilibrate at 10° C. for 15 min. after which time it was cooled to -20° C. 2,5-Difluorobenzyl chloride (9.73 g, 59.9 mmole) was added dropwise at a rate such as to maintain the reaction temperature at about -20° C. After complete addition the reaction mixture was warmed to 0° C. and allowed to react for 1 hr. The reaction appeared to be complete by GLC and was quenched with ice and water. The products were extracted into ether and dried over K2CO3. After filtration the solvent was removed under vacuum. The crystalline product was recrystallized from cyclohexane and dried, affording 10.5 g of 1-acetyl-4-ethynyl-4-(2,5-difluorophenylmethoxy)piperidine (35.8 mmole, 59.83%). This material appeared pure by GLC (99% on OV225, temperature program: 200° C. (2 min.), rate=25° C./min., 250° C. (15 min.), flow=30 ml/min. tR =4.00 min.) and by TLC on silica gel in hexane:ethylacetate (1:1), Rf =0.2. Mass Spec (ci MH+ =294),

1. temperatureafter which time it was cooled to -20° C
2. temperatureto maintain the reaction temperature at about -20° C
3. additionAfter complete addition the reaction mixture
4. temperaturewas warmed to 0° C.
5. customto react for 1 hr
6. customwas quenched with ice and water
7. extractionThe products were extracted into ether
8. dry with materialdried over K2CO3
9. filtrationAfter filtration the solvent
10. customwas removed under vacuum
11. customThe crystalline product was recrystallized from cyclohexane
12. customdried