4-Methylmorpholine → Ethyl 2-(2-((tert-butoxycarbonyl)amino)propanamido)-3-oxobutanoate

HRID 1930111노트

반응식

HRID 1930111 반응식
CN1CCOCC1.[C:8]([O:12][C:13]([NH:15][CH:16]([CH3:20])[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].ClC(OCC(C)C)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.[NH2:40][CH:41]([C:47](=[O:49])[CH3:48])[C:42]([O:44][CH2:45][CH3:46])=[O:43]>C1COCC1>[C:8]([O:12][C:13]([NH:15][CH:16]([CH3:20])[C:17]([NH:40][CH:41]([C:47](=[O:49])[CH3:48])[C:42]([O:44][CH2:45][CH3:46])=[O:43])=[O:19])=[O:14])([CH3:9])([CH3:10])[CH3:11]

참가 물질

6

반응물 4

HCID 79724-Methylmorpholine2회HCID 62365Isobutyl chloroformateHCID 2684712-N-Boc-aminopropionic acidHCID 86636663Butanoic acid, 2-amino-3-oxo-, ethyl ester, 4-methylbenzenesulfonate (1:1)

생성물 1

HCID 57992159Ethyl 2-(2-((tert-butoxycarbonyl)amino)propanamido)-3-oxobutanoate수율 68.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-25 °C

실험 절차

A solution of 4-methylmorpholine (900 g) in THF (15 L) was added to 2-(tert-butoxycarbonylamino)propanoic acid (1690 g, 8933.17 mmol). The mixture was cooled to −25° C. and isobutyl chloroformate (1.164 L, 8933.17 mmol) was added. After 20 minutes the second equivalent of 4-methylmorpholine (900 g) was added followed by ethyl 2-amino-3-oxobutanoate Tosylate salt (see J-P. Genet et al, Eur. J. Org. Chem., 2004, 3017-3026) (2700 g, 8507.78 mmol) suspended in THF (2.5 L). The mixture was stirred at −25° C. for 30 minutes and then left to warm to ambient temperature overnight. The reaction was quenched with water (15 L), extracted with EtOAc (3×5 L) and the combined extracts washed with 50% saturated brine (5 L). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford ethyl 2-(2-(tert-butoxycarbonylamino)propanamido)-3-oxobutanoate (1850 g, 68.7%).

후처리

  1. waitleft
  2. temperatureto warm to ambient temperature overnight
  3. customThe reaction was quenched with water (15 L)
  4. extractionextracted with EtOAc (3×5 L)
  5. washthe combined extracts washed with 50% saturated brine (5 L)
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by flash silica chromatography, elution gradient 50 to 80% EtOAc in isohexane
  11. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-ec8584dd9c77493fbd3557fc79beef21
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188092B2

반응 노트

불러오는 중…