Imidazole → (3R,4R)-benzyl 3-(tert-butoxycarbonylamino)-4-(tert-butyldimethylsilyloxy)piperidine-1-carboxylate

HRID 1920148Notes

Reaction equation

HRID 1920148 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@H:14]([OH:15])[CH2:13][CH2:12][N:11]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[CH3:31][C:32]([Si:35](Cl)([CH3:37])[CH3:36])([CH3:34])[CH3:33]>ClCCl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([NH:8][C@H:9]1[C@H:14]([O:15][Si:35]([C:32]([CH3:34])([CH3:33])[CH3:31])([CH3:37])[CH3:36])[CH2:13][CH2:12][N:11]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 53487823Benzyl (3R,4R)-3-(tert-butoxycarbonylamino)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 59455668(3R,4R)-benzyl 3-(tert-butoxycarbonylamino)-4-(tert-butyldimethylsilyloxy)piperidine-1-carboxylateYield 76%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (3R,4R)-benzyl 3-(tert-butoxycarbonylamino)-4-hydroxypiperidine-1-carboxylate (1.0 equiv.) in dichloromethane (0.1 M solution) was added imidazole (1.1 equiv.), DMAP (0.1 equiv.), and TBDMSCl (1.1 equiv.) sequentially. The reaction mixture was stirred at room temperature for 20 h. After worked up with dichloromethane, the crude material was purified by silica column chromatography (10% to 20% EtOAc in hexanes) yielding (3R,4R)-benzyl 3-(tert-butoxycarbonylamino)-4-(tert-butyldimethylsilyloxy)piperidine-1-carboxylate (76%). LCMS (m/z): 365.2 [(M-Boc)H+]; LC Rt=6.05 min.

Workup

  1. customthe crude material was purified by silica column chromatography (10% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1b6db5c68fef49519367b206c5fa5ce6
Source dataset
uspto-grants-2012_05
Patent number
US08168794B2

Reaction notes

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