Imidazole → (2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamide

HRID 470795ノート

反応式

HRID 470795 の反応式
[Cl:1][C:2]1[C:3]([CH3:27])=[C:4]([NH:10][C@H:11]([C@@H:24]([OH:26])[CH3:25])[C:12]([NH:14][CH2:15][C:16](=[O:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].CN(C=O)C.N1C=CN=C1.[C:38]([Si:42](Cl)([CH3:44])[CH3:43])([CH3:41])([CH3:40])[CH3:39]>CCOC(C)=O.O>[Si:42]([O:26][C@@H:24]([CH3:25])[C@@H:11]([NH:10][C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=1[CH3:27])[C:12]([NH:14][CH2:15][C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:13])([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:44])[CH3:43]

参加物

7

反応物 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 57908663(2R,3S)-2-(3-Chloro-4-cyano-2-methylphenylamino)-3-hydroxy-N-(2-oxo-2-phenylethyl)butanamide

生成物 1

HCID 57908587(2R,3S)-3-(tert-Butyldimethylsilyloxy)-2-(3-chloro-4-cyano-2-methylphenylamino)-N-(2-oxo-2-phenylethyl)butanamide収率 80.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A 500 mL round bottomed flask was charged with (2R,3S)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxy-N-(2-oxo-2-phenylethyl)butanamide (7.87 g, 20.4 mmol) and DMF (200 mL) then cooled to 0° C. Imidazole (6.94 g, 102 mmol) and tert-butylchlorodimethylsilane (9.22 g, 61.2 mmol) were added and the mixture was stirred and warmed to room temperature overnight. Water (200 mL) was added to the mixture followed by EtOAc (200 mL) and the phases partitioned. The organic phase was washed with water (2×100 mL), brine (100 mL), dried (Na2SO4) and concentrated to furnish the title compound as a white solid (8.2 g, 80%). 1H NMR (500 MHz, acetone-d6, δ in ppm) 7.97 (d, J=8 Hz, 2H), 7.44-7.66 (m, 1H), 0.40 (d, J=8 Hz, 1H), 6.42 (d, J=8 Hz, 1H), 5.43 (d, J=6 Hz, 1H), 4.77 (dd, J=6, 8 Hz, 2H), 4.79 (dd, J=5, 15 Hz, 2H), 4.70 (d, J=5, 15 Hz, 1H), 4.52-4.58 (m, 1H), 3.85-4.89 (m, 1H), 2.39 (s, 3H), 1.24 (d, J=6 Hz, 3H).

後処理

  1. temperaturewarmed to room temperature overnight
  2. customthe phases partitioned
  3. washThe organic phase was washed with water (2×100 mL), brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-8e7edea6f1684785aa506bd0a742448e
出典データセット
uspto-grants-2014_01
特許番号
US08629167B2

反応ノート

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