Hydrochloric Acid → 1-methylethyl (2E)-2-butenoylcarbamate

온도

-30 °C

Isopropyl carbamate (30 g, 291 mmol, available from TCI) was charged to a 3 L Lara vessel and dry THF (150 ml) added. (2E)-2-Butenoyl chloride (31.2 ml, 326 mmol, available from Aldrich) was added under nitrogen and the jacket cooled to −30° C. When the solution temperature reached −17° C. lithium tert-butoxide (1M, 655 ml, 655 mmol) was added by peristaltic pump over 2 h, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was stirred for 30 min and brought to 0° C. Diethyl ether (450 ml) and hydrochloric acid (1M, 375 ml) were added and the mixture brought to 20° C. with vigorous stirring. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. Brine (375 ml) was added and the mixture stirred vigourously. The stirring was stopped, the layers allowed to separate and the aqueous layer run off. The organic layer was dried (MgSO4), filtered and evaporated to a brown oil (60 g). The oil was applied to a silica column (40+M Biotage) and eluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV). The product containing fractions were evaporated to dryness and loaded on to a silica column (1500 g, Redisep Isco) and eluted with a ethyl acetate in cyclohexane gradient (0-40%). The clean, product containing fractions were evaporated to an off-white solid (15.41 g). LCMS (Method C), Rt 0.68, MH+ 172

1. additionadded
2. customreached −17° C.
3. additionwas added by peristaltic pump over 2 h
4. customthe reaction temperature between −10° C. and −18° C
5. additionOnce the addition
6. custombrought to 0° C
7. custombrought to 20° C. with vigorous stirring
8. customto separate
9. additionBrine (375 ml) was added
10. stirringthe mixture stirred vigourously
11. customto separate
12. dry with materialThe organic layer was dried (MgSO4)
13. filtrationfiltered
14. customevaporated to a brown oil (60 g)
15. washeluted with DCM/ethyl acetate (1:1 to 0:1, 10 CV)
16. additionThe product containing fractions
17. customwere evaporated to dryness
18. washeluted with a ethyl acetate in cyclohexane gradient (0-40%)
19. additionThe clean, product containing fractions
20. customwere evaporated to an off-white solid (15.41 g)

ORD 기록

ord-636de502d912487890034e00dee6351b

출처 데이터셋

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09315487B2