Imidazole → Benzyl trans(+/-)-4-[(tert-butoxycarbonyl)amino]-3-{[tert-butyl(dimethyl)silyl]oxy}piperidine-1-carboxylate

HRID 921643노트

반응식

HRID 921643 반응식
[C:1]([Si:5]([CH3:8])([CH3:7])Cl)([CH3:4])([CH3:3])[CH3:2].[C:9]([O:13][C:14]([NH:16][C@@H:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH2:19][C@H:18]1[OH:33])=[O:15])([CH3:12])([CH3:11])[CH3:10].N1C=CN=C1>CN(C=O)C>[C:9]([O:13][C:14]([NH:16][C@@H:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH2:19][C@H:18]1[O:33][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:8])[CH3:7])=[O:15])([CH3:12])([CH3:10])[CH3:11]

참가 물질

5

반응물 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 58745562(3R,4R)-Benzyl 4-((tert-butoxycarbonyl)amino)-3-hydroxypiperidine-1-carboxylate

생성물 1

HCID 60200764Benzyl trans(+/-)-4-[(tert-butoxycarbonyl)amino]-3-{[tert-butyl(dimethyl)silyl]oxy}piperidine-1-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

tert-butyldimethylchlorosilane (6.51 g, 43.2 mmol) was added to a solution of (+/−)(3R,4R)-benzyl 4-((tert-butoxycarbonyl)amino)-3-hydroxypiperidine-1-carboxylate (prepared according to a published literature procedure: Fink, Brian, et al., WO 2005/066176, 10.1 g, 28.8 mmol) and imidazole (3.92 g, 57.6 mmol) in DMF (60 mL). The mixture was stirred at room temperature overnight. Ice water was added and the reaction mixture was extracted with ether twice, the combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (330 g column, eluting with 5-20% ethyl acetate/dichloromethane) to give (+/−)-(3R,4R)-benzyl 4-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)piperidine-1-carboxylate (13.3 g) as a white solid.

후처리

  1. customprepared
  2. extractionthe reaction mixture was extracted with ether twice
  3. washthe combined extracts were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customthe crude product was purified by flash chromatography on silica gel using
  8. washan automated ISCO system (330 g column, eluting with 5-20% ethyl acetate/dichloromethane)

출처 및 근거

ORD 기록
ord-0d44b67529e44c09851173bbf6f35e01
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09273057B2

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