Potassium Carbonate → tert-Butyl 4-[4-(3-methoxy-3-oxopropyl)piperidin-1-yl]benzoate

HRID 446559Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH2:3][CH2:2]1.F[C:14]1[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH3:12][O:11][C:9](=[O:10])[CH2:8][CH2:7][CH:4]1[CH2:5][CH2:6][N:1]([C:14]2[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])=[CH:16][CH:15]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 120 °C

Procedure

Methyl 3-(piperidin-4-yl)propanoate (WO2004/92124 A2) (206 mg, 1.11 mmol) was dissolved in N,N-dimethylformamide (10 mL), tert-butyl 4-fluorobenzoate (141 mg, 1.11 mmol) and potassium carbonate (100 mg, 1.11 mmol) were added, and the mixture was stirred at 120° C. under a nitrogen atmosphere for 16 hours. After the reaction was completed, a saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate, 10:1, v/v) to give the title compound (126 mg; yield, 31%) as a colorless oily substance.

Workup

customto separate the layers
customThe resulting organic layer was separated
washwashed with saturated sodium chloride solution
dry with materialdried with anhydrous sodium sulfate
customthe solvent was evaporated under reduced pressure
customThe residue was purified by NH silica gel column chromatography (hexane

Sources & evidence

ORD record: ord-42346772ca714dc69f0744d71a88a445
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08476253B2

Reaction notes

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