Isopropyl chloroformate → Isopropyl 4-Hydroxypiperidine-1-carboxylate

Temperature

20 °C

To a stirred mixture of 4-hydroxypiperidine (53.8 g, 1.000 eq), triethylamine (71.8 g, 1.334 equivalents), and ethyl acetate (498.8 g) was added neat isopropyl chloroformate (78.0 g, 1.1966 equivalents) at a rate sufficiently slow to maintain the reaction mixture temperature at 10°-17° C. with reactor jacket cooling. After the addition had been completed, the reaction mixture was stirred at 20° C. for 18 hours. Then water (100 g) was added, and the resulting mixture was stirred for 15 minutes before the phases were separated. The organic phase was washed with two 100-gram-portions of 20 wt % aqueous NaCl by stirring for 15 min at 150 rpm before separating the aqueous wash. After a final wash with water (100 g), the organic phase was concentrated by distillation on a rotary evaporator at reduced pressure to provide product (2) (91.1 g, 92.0% yield) as light amber oil of 96.8% purity by GC. Distillation of this crude product at 117-120° C., 0.3-1.0 torr gave a 95.7% recovery of product (2) as a colorless oil collected at 112°-119° C.

1. temperatureto maintain the reaction mixture temperature at 10°-17° C. with reactor jacket
2. temperaturecooling
3. additionAfter the addition
4. stirringthe resulting mixture was stirred for 15 minutes before the phases
5. customwere separated
6. washThe organic phase was washed with two 100-gram-portions of 20 wt % aqueous NaCl
7. stirringby stirring for 15 min at 150 rpm
8. custombefore separating the aqueous wash
9. washAfter a final wash with water (100 g)
10. concentrationthe organic phase was concentrated by distillation on a rotary evaporator at reduced pressure

ORD record

ord-af58ea6c39ae40359985fd41cea74561

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812159B2