2-Bromoethanol → Methyl(3S,4R)-4-{[(benzyloxy)carbonyl]amino}-1-(2-hydroxyethyl)piperidine-3-carboxylate

HRID 1644312Notes

Reaction equation

[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][NH:15][CH2:14][C@@H:13]1[C:18]([O:20][CH3:21])=[O:19])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.Br[CH2:32][CH2:33][OH:34]>C(#N)C>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]1[CH2:17][CH2:16][N:15]([CH2:32][CH2:33][OH:34])[CH2:14][C@@H:13]1[C:18]([O:20][CH3:21])=[O:19])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of methyl(3S,4R)-4-{[(benzyloxy)carbonyl]amino}piperidine-3-carboxylate (WO 2005/066176) (2.29 g, 7.83 mmol), N,N-diisopropylethylamine (2.05 mL, 11.75 mmol and 2-bromoethanol (0.722 mL, 10.18 mmol) in dry acetonitrile (17 mL) was heated in the microwave at 70° C. for 4.5 hours. The solvent was removed under reduced pressure and the residue taken up in ethyl acetate (200 mL) and washed with saturated aqueous sodium hydrogencarbonate solution (100 mL). The aqueous phase was back extracted once with ethyl acetate (100 mL) and the combined organic phases were dried over sodium sulfate. Chromatography on silica gel with dichloromethane/methanol (12:1) gave 2.0 g (76%), mp 73° C.

Workup

customThe solvent was removed under reduced pressure
washwashed with saturated aqueous sodium hydrogencarbonate solution (100 mL)
extractionThe aqueous phase was back extracted once with ethyl acetate (100 mL)
dry with materialthe combined organic phases were dried over sodium sulfate
customChromatography on silica gel with dichloromethane/methanol (12:1) gave 2.0 g (76%), mp 73° C.

Sources & evidence

ORD record: ord-b3ede395496f40239e525777266fb079
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08124602B2

Reaction notes

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