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

HRID 1028613노트

반응식

HRID 1028613 반응식
[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]

참가 물질

7

반응물 4

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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-352671b6d07648659b6a3880b12ae59a
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08735435B2

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