Imidazole → benzyl ((1S,2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate

HRID 1994583ノート

反応式

HRID 1994583 の反応式
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CN=C1.[C:14]([CH:16]([OH:30])[C@@H:17]([NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:18])#[N:15].O>C(Cl)Cl>[Si:1]([O:30][C@@H:16]([C:14]#[N:15])[C@@H:17]([NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si:1]([O:30][C@H:16]([C:14]#[N:15])[C@@H:17]([NH:19][C:20](=[O:29])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:18])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 86603429benzyl [(1S)-2-cyano-2-hydroxy-1-methylethyl]carbamate

生成物 2

HCID 86603430benzyl ((1S,2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamateHCID 86603431benzyl ((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

tert-Butyldimethylsilyl chloride (471 mg, 3.12 mmol) and imidazole (483 mg, 7.10 mmol) were added successively to a stirred solution of benzyl [(1S)-2-cyano-2-hydroxy-1-methylethyl]carbamate (665 mg, 2.84 mmol) in dry CH2Cl2 (13 mL) at room temperature under N2 and the mixture was stirred overnight. Water (30 mL) was added and the mixture was extracted with Et2O (3×30 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-15% EtOAc in hexanes gradient) to afford benzyl ((1S,2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate and benzyl ((1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-cyano-1-methylethyl)carbamate. (1S,2R)-diastereoisomer: Rf=0.29 (10% EtOAc in hexanes). LCMS calc.=349.2; found=349.1 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.39-7.33 (m, 5H), 5.16 (d, J=12.1 Hz, 1H), 5.07 (d, J=12.1 Hz, 1H), 4.89 (br d, J=6.6 Hz, 1H), 4.68 (br, d, 3.6 Hz, 1H), 3.92 (m, 1H), 1.31 (d, J=6.7 Hz, 3H), 0.91 (s, 9H), 0.21 (s, 3H), 0.17 (s, 3H). (1S,2S)-diastereoisomer: Rf=0.24 (10% EtOAc in hexanes). LCMS calc.=349.2; found=349.1 (M+1)+. 1H NMR (500 MHz, CDCl3) δ 7.38-7.32 (m, 5H), 5.10 (s, 2H), 4.76 (br d, J=6.9 Hz, 1H), 4.63 (br s, 1H), 4.00 (m, 1H), 1.31 (d, J=6.8 Hz, 3H), 0.90 (d, J=2.9 Hz, 9H), 0.17 (s, 3H), 0.08 (s, 3H).

後処理

  1. extractionthe mixture was extracted with Et2O (3×30 mL)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by flash chromatography (Si, 40×160 mm, 0-15% EtOAc in hexanes gradient)

出典と根拠

ORDレコード
ord-fc9d1bd9bda44bfaafa971bcbef41b80
出典データセット
uspto-grants-2010_01
特許番号
US07652049B2

反応ノート

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