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

HRID 907633Notes

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 over MgSO4, 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 over MgSO4
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-05c143653f7647d5be4c565126942c25
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08013152B2

Reaction notes

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