Imidazole → HCID 95757513, compound

HRID 15338Notes

Reaction equation

HRID 15338 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH:3]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].[C:20]([Si:24]([CH3:27])([CH3:26])Cl)([CH3:23])([CH3:22])[CH3:21].N1C=CN=C1.O>CN(C)C=O.C(OCC)(=O)C.CCCCCC>[OH:1][C@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:4][C@H:3]1[C:15]([O:17][CH2:18][CH3:19])=[O:16].[CH3:21][C:20]([Si:24]([CH3:27])([CH3:26])[O:1][C@@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:4][C@H:3]1[C:15]([O:17][CH2:18][CH3:19])=[O:16])([CH3:23])[CH3:22]

Participants

9

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 563051HCID 563051, compound

Product 2

HCID 95757513HCID 95757513, compoundYield 45%HCID 131728172HCID 131728172, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of racemic ethyl 4-hydroxy-1-(phenylmethyl)-3-piperidinecarboxylate (37 g, 140 mmol) in N,N-dimethylformamide (250 ml) was added tert-butyldimethylchlorosilane (10.6 g, 70 mmol) and imidazole (5.3 g, 77 mmol) under argon. The reaction was stirred at room temperature for 3 h; water was added and the aqueous phase was extracted with dichloromethane. The organic layer was dried and the solvent was removed under reduced pressure to afford 40 g of crude. The crude was divided into 3 batches (5 g, 17 g, 17 g) and each batch was subjected to column chromatography on silica gel using a hexane and ethyl acetate gradient (0-20% ethyl acetate in hexane). This provided the desired compound (16.67 g, 45%) and ethyl(trans)-4-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-(phenylmethyl)-3-piperidinecarboxylate (15.8 g, 30%).

Workup

  1. extractionthe aqueous phase was extracted with dichloromethane
  2. customThe organic layer was dried
  3. customthe solvent was removed under reduced pressure
  4. customto afford 40 g of crude

Sources & evidence

ORD record
ord-3e4c6f8c05484255b4231280494c249b
Source dataset
uspto-grants-2010_06
Patent number
US07732461B2

Reaction notes

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