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Acetic Anhydride → (2R,5R)-5-[(1S,2S)-2-Acetylamino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20363
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HRID 20363 반응식
C(N(CC)CC)C.[C:8]([O:12][C:13]([N:15]1[C@@H:20]([C@@H:21]([OH:33])[C@@H:22]([NH2:32])[CH2:23][C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)[CH2:19][O:18][C@@H:17]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].[C:40](OC(=O)C)(=[O:42])[CH3:41]>O1CCCC1.ClCCl>[C:8]([O:12][C:13]([N:15]1[C@@H:20]([C@@H:21]([OH:33])[C@@H:22]([NH:32][C:40](=[O:42])[CH3:41])[CH2:23][C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([Cl:31])[CH:25]=2)[CH2:19][O:18][C@@H:17]([O:34][CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:16]1)=[O:14])([CH3:10])([CH3:9])[CH3:11]
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참가 물질

6

반응물 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 68561142(2R,5R)-5-[(1S,2S)-2-Amino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester

생성물 1

HCID 68560377(2R,5R)-5-[(1S,2S)-2-Acetylamino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester수율 45.5%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

Add triethylamine (138 μL, 0.99 mmol) to a solution of (2R,5R)-5-[(1S,2S)-2-amino-3-(3-chloro-5-fluorophenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-morpholine-4-carboxylic acid tert-butyl ester (0.428 g, 0.901 mmol) in tetrahydrofuran (5 mL) followed by acetic anhydride (91 μL, 0.991 mmol). Stir at room temperature for 30 minutes, dilute with dichloromethane, wash with 0.1 N hydrochloric acid (30 mL), saturated aqueous sodium chloride (30 mL), dry (sodium sulfate), filter and purify (silica gel chromatography, eluting with 2:98 to 10:90 methanol:dichloromethane) to give the title compound as a white foam (0.212 g, 45%).

후처리

  1. washwash with 0.1 N hydrochloric acid (30 mL), saturated aqueous sodium chloride (30 mL)
  2. dry with materialdry (sodium sulfate)
  3. filtrationfilter
  4. custompurify
  5. wash(silica gel chromatography, eluting with 2:98 to 10:90 methanol:dichloromethane)

출처 및 근거

ORD 기록
ord-27f93aa80efa489dbe290ee599eb253f
출처 데이터셋
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07745438B2

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