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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
ノート
印刷プレビュー

反応式

HRID 20335 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 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

生成物 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 ester収率 85.4%

試薬・触媒・溶媒 1

HCID 8028
Tetrahydrofuran
溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-9134fb0a44d14ed7b7ac6d0e074d8dd3
出典データセット
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07745438B2

反応ノート

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