Phosgene → (3s)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1r)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 750378

반응식

HRID 750378 반응식
[C:1](Cl)(Cl)=[O:2].[CH3:5][C:6]1([CH3:13])[C@H:11]([OH:12])[C:9](=[O:10])[O:8][CH2:7]1.N1C2C(=CC=CC=2)C=CC=1.C(N(CC)CC)C.[NH2:31][C@@H:32]([CH2:46][CH2:47][CH2:48][CH3:49])[CH:33]([OH:45])[C:34]([NH:36][C@@H:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH3:38])=[O:35]>O1CCCC1>[OH:45][CH:33]([C@@H:32]([NH:31][C:1](=[O:2])[O:12][C@H:11]1[C:6]([CH3:13])([CH3:5])[CH2:7][O:8][C:9]1=[O:10])[CH2:46][CH2:47][CH2:48][CH3:49])[C:34](=[O:35])[NH:36][C@@H:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH3:38]

참가 물질

7

반응물 5

HCID 6371PhosgeneHCID 7047QuinolineHCID 8471TriethylamineHCID 736053(+)-PantolactoneHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide

생성물 1

HCID 91135603(3s)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1r)-1-phenylethyl]amino}ethyl)pentylcarbamate수율 85.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

Phosgene (1.04 mL, 1.93 M, 2.00 mmol) was added dropwise to a solution of (S)-(+)-pantolactone (130 mg, 1.00 mmol) and quinoline (0.241 mL, 2.00 mmol) in anhydrous tetrahydrofuran (3 mL) at 0° C. under nitrogen. The cold bath was removed, and the mixture was stirred for 18 h at room temperature. Volatiles were then removed under vacuum, and the resulting solid was slurried in anhydrous tetrahydrofuran (4 mL) under nitrogen. A solution of triethylamine (0.153 mL, 1.10 mmol) and (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide (264 mg, 1.00 mmol) in anhydrous tetrahydrofuran was added. The resulting mixture was stirred for 18 h, and was then partitioned between ethyl acetate (70 mL) and 1 N hydrochloric acid (35 mL). The ethyl acetate layer was washed further with two 35 mL portions of 1 N hydrochloric acid, followed by saturated aqueous sodium chloride (35 mL). After drying over magnesium sulfate, volatiles were removed to afford (3S)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a tan oil (358 mg, 85%).

후처리

  1. customThe cold bath was removed
  2. customVolatiles were then removed under vacuum
  3. stirringThe resulting mixture was stirred for 18 h
  4. customwas then partitioned between ethyl acetate (70 mL) and 1 N hydrochloric acid (35 mL)
  5. washThe ethyl acetate layer was washed further with two 35 mL portions of 1 N hydrochloric acid
  6. dry with materialAfter drying over magnesium sulfate, volatiles
  7. customwere removed

출처 및 근거

ORD 기록
ord-827e5a6be30e4be79a7221af68c7c399
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07402606B2

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