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

HRID 882225

반응식

HRID 882225 반응식
[C:1](=[O:7])([O:3][CH:4]([CH3:6])[CH3:5])[NH2:2].[C:8](Cl)(=[O:12])/[CH:9]=[CH:10]/[CH3:11].CC(C)([O-])C.[Li+].Cl>C(OCC)C.O1CCCC1>[C:8]([NH:2][C:1](=[O:7])[O:3][CH:4]([CH3:6])[CH3:5])(=[O:12])/[CH:9]=[CH:10]/[CH3:11]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 15628Isopropyl carbamateHCID 643131trans-Crotonyl chlorideHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

생성물 1

HCID 866691361-methylethyl (2E)-2-butenoylcarbamate

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
-30 °C

실험 절차

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. 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 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 vigorously. 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 was applied to a silica column (40+M Biotage) and eluted with DCM/EtOAc (1:1 to 0:1, 10CV). The product containing fractions were evaporated to dryness and loaded on to a Redisep Isco silica column (1500 g) and eluted with a EtOAc 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

후처리

  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 vigorously
  10. customto separate
  11. dry with materialThe organic layer was dried (MgSO4)
  12. filtrationfiltered
  13. customevaporated to a brown oil (60 g)
  14. washeluted with DCM/EtOAc (1:1 to 0:1, 10CV)
  15. additionThe product containing fractions
  16. customwere evaporated to dryness
  17. washeluted with a EtOAc in cyclohexane gradient (0-40%)
  18. additionThe clean, product containing fractions
  19. customwere evaporated to an off-white solid (15.41 g)

출처 및 근거

ORD 기록
ord-3a253191f5784f95b3a91688ed51045e
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993554B2

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