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Sodium Iodide → (R)-4-[(1S,2S)-2-Acetylamino-1-benzyloxy-3-(3,5-difluoro-phenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20335
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인쇄 미리보기

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HRID 20335 반응식
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([OH:28])[C@@H:14]([NH:24][C:25](=[O:27])[CH3:26])[CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:30])[CH3:29])=[O:7])([CH3:4])([CH3:3])[CH3:2].[I-].[Na+].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([O:28][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@@H:14]([NH:24][C:25](=[O:27])[CH3:26])[CH2:15][C:16]2[CH:21]=[C:20]([F:22])[CH:19]=[C:18]([F:23])[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:30])[CH3:29])=[O:7])([CH3:4])([CH3:2])[CH3:3]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 5238Sodium IodideHCID 7498Benzyl BromideHCID 68562048(R)-4-[(1S,2S)-2-Acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

생성물 1

HCID 68561152(R)-4-[(1S,2S)-2-Acetylamino-1-benzyloxy-3-(3,5-difluoro-phenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester수율 85.4%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

실험 절차

Suspend (R)-4-[(1S,2S)-2-acetylamino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (4.78 g, 11.2 mmol) in dry tetrahydrofuran (115 ml) under a nitrogen atmosphere and add sodium hydride NaH (60% weight dispersion in mineral oil, 1.17 g, 29.3 mmol). Stir the resulting mixture for 30 minutes and then add sequentially sodium iodide (600 mg, 4.0 mmol) and benzyl bromide (2.7 mL, 22.7 mmol). Stir the resulting mixture for 2.5 hours and then quench by the addition of a 1:1 mixture of saturated aqueous ammonium chloride and saturated aqueous sodium chloride. Dilute the resulting mixture with ethyl acetate and discard the aqueous phase. Wash the organic phase with saturated aqueous sodium chloride, dry over magnesium sulfate, filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes) to give the desired compound as a white foam (4.96 g, 85%).

후처리

  1. stirringStir the resulting mixture for 2.5 hours
  2. customquench by the addition of a 1:1 mixture of saturated aqueous ammonium chloride and saturated aqueous sodium chloride
  3. additionDilute the resulting mixture with ethyl acetate
  4. washWash the organic phase with saturated aqueous sodium chloride
  5. dry with materialdry over magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. custompurify
  9. wash(silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes)

출처 및 근거

ORD 기록
ord-9134fb0a44d14ed7b7ac6d0e074d8dd3
출처 데이터셋
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07745438B2

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