Potassium Carbonate → 5-[(3-Benzyl)-1-piperidinyl]valeric acid methyl ester

HRID 324538Notes

Reaction equation

Cl.[CH2:2]([CH:9]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:16][CH2:17][CH2:18][CH2:19][C:20]([O:22][CH3:23])=[O:21].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.C(OCC)C>[CH3:23][O:22][C:20](=[O:21])[CH2:19][CH2:18][CH2:17][CH2:16][N:11]1[CH2:12][CH2:13][CH2:14][CH:9]([CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[CH2:10]1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 3-benzylpiperidine hydrochloride (2 g, 9.4 mmol) in DMF (40 mL) were added methyl 5-bromovalerate (1.6 mL, 11.3 mmol) and potassium carbonate (3.2 g, 23.6 mmol). This heterogeneous mixture was heated at 110° C. for 1 hr then cooled at 25° C., diluted with water (200 mL) and diethyl ether (200 mL). The aqueous solution was extracted with diethyl ether (100 mL) and the collected organic phase was washed with brine (200 mL), dried and concentrated in vacuum. The crude compound was purified by silica gel column chromatography using CH2Cl2/MeOH as eluant to afford the title compound as an oil (1.76 g, 65%). 1H-NMR (CDCl3): 0.8-1.0 (m, 1H); 1.4-1.7 (m, 8H); 1.8-1.95 (m, 2H); 2.25-2.35 (m, 4H); 2.4-2.6 (m, 2H); 2.75-2.9 (m, 2H); 3.65 (s, 3H); 7.132 (d, J=7.0, 2H); 7.186 (d, J=7.2, 1H); 7.264 (t, J=7.2, 2H).

Workup

temperaturethen cooled at 25° C.
extractionThe aqueous solution was extracted with diethyl ether (100 mL)
washthe collected organic phase was washed with brine (200 mL)
customdried
concentrationconcentrated in vacuum
customThe crude compound was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-455484e8376c4384955d1414731785c8
Source dataset: uspto-grants-2001_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06218404B1

Reaction notes

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