Methyl 3-bromopropanoate → Methyl 3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionate

HRID 2193565Notes

Reaction equation

Br[CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5].[NH:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15](=[O:29])[NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:10][CH2:9]1.CCN(C(C)C)C(C)C>C(#N)C>[CH3:7][O:6][C:4](=[O:5])[CH2:3][CH2:2][N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15](=[O:29])[NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:12][CH2:13]1

Participants

Conditions

Temperature: 50 °C

Procedure

Methyl 3-bromopropionate (553 μL, 5.07 mmol) was added to a stirred solution of biphenyl-2-ylcarbamic acid piperidin-4-yl ester (1.00 g, 3.38 mmol; prepared as described in Preparation 1) and DIPEA (1.76 mL, 10.1 mmol) in ACN (34 mL) at 50° C. and the reaction mixture was heated at 50° C. overnight. The solvent was then removed under reduced pressure, and the residue was dissolved in DCM (30 mL). The resulting solution was washed with saturated aqueous sodium bicarbonate solution (10 mL), dried (magnesium sulfate), filtered and the solvent was removed under reduced pressure. The crude residue was purified by column chromatography (5-10% MeOH/DCM) to give 905 mg of the title intermediate (70% yield).

Workup

customThe solvent was then removed under reduced pressure
dissolutionthe residue was dissolved in DCM (30 mL)
washThe resulting solution was washed with saturated aqueous sodium bicarbonate solution (10 mL)
dry with materialdried (magnesium sulfate)
filtrationfiltered
customthe solvent was removed under reduced pressure
customThe crude residue was purified by column chromatography (5-10% MeOH/DCM)

Sources & evidence

ORD record: ord-c8b92a8b077c4fbeb7f41978c4b73d5d
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329911B2

Reaction notes

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