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

HRID 1430812Notes

Reaction equation

HRID 1430812 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-808592c66f2548dea535d7f219a73bfb
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

Loading…