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

온도

-30 °C

Isopropyl carbamate (30 g, 291 mmol, available from TCl) was charged to a 3 L Lara vessel and dry Tetrahydrofuran (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. 1M Lithium tert-butoxide (655 ml, 655 mmol) was added by peristaltic pump over 2 hours, keeping the reaction temperature between −10° C. and −18° C. Once the addition was complete the mixture was complete the mixture was stirred for 30 mins and brought to 0° C. Diethyl ether (450 ml) and 1M HCl (375 ml) were added and the mixture brought to 20° C. with vigourous 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 (magnesium sulfate), filtered and evaporated to a brown oil (60 g). The mixture was loaded on to a 40+M Biotage silica column 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 1500 g Redisep Isco silica column and eluted with a gradient of 0 to 40% ethyl acetate in cyclohexane. 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. customthe reaction temperature between −10° C. and −18° C
4. additionOnce the addition
5. custombrought to 0° C
6. custombrought to 20° C. with vigourous stirring
7. customto separate
8. additionBrine (375 ml) was added
9. stirringthe mixture stirred vigourously
10. customto separate
11. dry with materialThe organic layer was dried (magnesium sulfate)
12. filtrationfiltered
13. customevaporated to a brown oil (60 g)
14. washeluted with DCM:ethyl acetate (1:1 to 0:1, 10 CV)
15. additionThe product containing fractions
16. customwere evaporated to dryness
17. washeluted with a gradient of 0 to 40% ethyl acetate in cyclohexane
18. additionThe clean, product containing fractions
19. customwere evaporated to an off white solid (15.41 g)

ORD 기록

ord-06fb734b1ac7457ea0547f70ccef3715

출처 데이터셋

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09360482B2