Lithium Hexamethyldisilazide → (1S,5S)-7-Hydroxy-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

HRID 1917343노트

반응식

HRID 1917343 반응식
[C:1]([O:5][C:6]([C:8]1([CH2:22][CH:23]2[CH2:25][O:24]2)[CH2:12][C:11](=[O:13])[N:10]([C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>O1CCCC1>[C:1]([O:5][C:6]([C@@:8]12[CH2:22][CH:23]([OH:24])[CH2:25][C@@H:12]1[C:11](=[O:13])[N:10]([C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[CH2:9]2)=[O:7])([CH3:2])([CH3:4])[CH3:3]

참가 물질

4

반응물 2

HCID 2733832Lithium HexamethyldisilazideHCID 86664649HCID 86664649, 화합물

생성물 1

HCID 67491063(1S,5S)-7-Hydroxy-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester수율 26%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

3-(Oxiran-2-ylmethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (4.2 g, 12.16 mmol) was dissolved in tetrahydrofuran (50 mL). A 1 M solution of lithium hexamethyldisilazide in tetrahydrofuran (18 mL, 1.5 equivalents) was added in an argon atmosphere at −78° C., and the mixture was gradually heated. When the reaction temperature reached about room temperature, the reaction was quenched with an ammonium chloride solution, followed by extraction with ethyl acetate. The extract was dried over magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1→2:1→1:1→1:2) to give 1.07 g (26%) of the title compound having a single isomer as a colorless oil. 1.0 g (24%) of the raw material was collected. 1.20 g (29%) of a four-membered ring-closed compound as a by-product was obtained as a diastereomer mixture.

후처리

  1. temperaturethe mixture was gradually heated
  2. customreached about room temperature
  3. customthe reaction was quenched with an ammonium chloride solution
  4. extractionfollowed by extraction with ethyl acetate
  5. dry with materialThe extract was dried over magnesium sulfate
  6. filtrationAfter filtration
  7. customthe solvent was evaporated under reduced pressure
  8. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1→2:1→1:1→1:2)

출처 및 근거

ORD 기록
ord-81ca90c1e9cc449a97ce6729d18a0618
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618094B2

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