Sodium hydride → Methyl 2-[(tert-butoxycarbonyl)amino]-4-cyano-4-(2,3-difluorophenyl)butanoate

HRID 340163ノート

反応式

HRID 340163 の反応式
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]#[N:11].[H-].[Na+].[C:14]([O:18][C:19]([NH:21][C@@H:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:23]I)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[C:14]([O:18][C:19]([NH:21][CH:22]([CH2:23][CH:9]([C:10]#[N:11])[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[F:1])[C:25]([O:27][CH3:28])=[O:26])=[O:20])([CH3:17])([CH3:16])[CH3:15]

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 5189682,3-DifluorophenylacetonitrileHCID 11416215(S)-Methyl 2-Boc-amino-3-iodopropionate

生成物 1

HCID 68748709Methyl 2-[(tert-butoxycarbonyl)amino]-4-cyano-4-(2,3-difluorophenyl)butanoate収率 55.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (2,3-difluorophenyl)acetonitrile (18.6 g, 122 mmol) in N,N-dimethylformamide (243 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil) (4.37 g, 109 mmol). After 20 min, methyl N-(tert-butoxycarbonyl)-3-iodo-D-alaninate (20.0 g, 60.8 mmol) was added, and the resulting mixture stirred 50 min. Saturated aqueous sodium bicarbonate was added, and the mixture was warmed to ambient temperature. Water was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with water (3×), brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→20% hexanes/ethyl acetate) gave the title compound (12.0 g). MS 377.3 (M+Na).

後処理

  1. extractionthe mixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with water (3×), brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% hexanes→20% hexanes/ethyl acetate)

出典と根拠

ORDレコード
ord-c4c75bd3fd94489b8fc0f555ab62ba67
出典データセット
uspto-grants-2014_11
特許番号
US08895572B2

反応ノート

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