Potassium Carbonate → 1-(2-{2-[3-(3-Fluorophenyl)piperidin-1-yl]ethyl}phenyl)piperidin-2-one

HRID 2178519Notes

Reaction equation

Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][CH2:12][NH:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.C([O-])([O-])=O.[K+].[K+].CC1C=CC(S(O[CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[N:40]2[CH2:45][CH2:44][CH2:43][CH2:42][C:41]2=[O:46])(=O)=O)=CC=1>C(#N)C>[F:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][CH2:12][N:11]([CH2:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[N:40]3[CH2:45][CH2:44][CH2:43][CH2:42][C:41]3=[O:46])[CH2:10]2)[CH:6]=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 85 °C

Procedure

3-(3-Fluorophenyl)piperidine hydrochloride a2-4 (432 mg, 2 mmol, 1 eq) and K2CO3 (829 mg, 6 mmol, 3 eq) are added to a solution 2-[2-(2-oxopiperidin-1-yl)phenyl]ethyl 4-methylbenzenesulfonate a2-3 (747 mg, 2 mmol, 1 eq) in acetonitrile (10 ml). The reaction mixture is stirred at 85° C. overnight, then filtered and the filtrate is condensed under reduced pressure. The residue is purified by basic reverse phase chromatography over silicagel (gradient CH3CN/H2O/NH4OH from 50/50/0.1 to 80/20/0.1) to afford 472 mg (1.24 mmol) of 1-(2-{2-[3-(3-fluorophenyl)piperidin-1-yl]ethyl}phenyl)piperidin-2-one as a free base. Oxalic acid (111 mg, 1.24 mmol, 1 eq) is added to the residue dissolved in diethylether. The precipitate obtained is filtered and dried under vacuum to afford 517 mg of 1-(2-{2-[3-(3-fluorophenyl)piperidin-1-yl]ethyl}phenyl)piperidin-2-one oxalate 24.

Workup

filtrationfiltered
customcondensed under reduced pressure
customThe residue is purified by basic reverse phase chromatography over silicagel (gradient CH3CN/H2O/NH4OH from 50/50/0.1 to 80/20/0.1)

Sources & evidence

ORD record: ord-f0b38fbdb6f44e16b40b9de42af6c13e
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067930B2

Reaction notes

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