Potassium Carbonate → (3R,4S)-N-benzyl-3-fluoro-1-(3-methoxy-4-nitrophenyl)piperidin-4-amine

HRID 1256017Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].F[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]([O:17][CH3:18])[CH:9]=1.Cl.[CH2:20]([NH:27][C@H:28]1[CH2:33][CH2:32][NH:31][CH2:30][C@H:29]1[F:34])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CC(N(C)C)=O>[CH2:20]([NH:27][C@H:28]1[CH2:33][CH2:32][N:31]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[C:10]([O:17][CH3:18])[CH:9]=2)[CH2:30][C@H:29]1[F:34])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

Conditions

Temperature: 120 °C

Procedure

DMA (60 ml) and potassium carbonate (5.65 g, 40.86 mmol) were added to the flask containing 4-fluoro-2-methoxy-1-nitrobenzene (1.748 g, 10.22 mmol) and (3R,4S)—N-benzyl-3-fluoropiperidin-4-amine HCl salt (INTERMEDIATE 46, 2.5 g, 10.22 mmol). The reaction was heated to 120° C. for 5 h. The reaction mixture was cooled to rt, and filtered. The filtrate was diluted with EtOAc (50 ml) and the solution was washed with brine (2×100 ml). The organic layer was dried over Na2SO4, filtered, and concentrated to give a crude yellow liquid. It was purified using silica gel chromatography (80-100% EtOAc/hexane) to give the title product (2.200 g, 59.9%). m/z 361.

Workup

temperatureThe reaction mixture was cooled to rt
filtrationfiltered
additionThe filtrate was diluted with EtOAc (50 ml)
washthe solution was washed with brine (2×100 ml)
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto give a crude yellow liquid
customIt was purified

Sources & evidence

ORD record: ord-2aa222eb24cd4d01a6d12033156e9544
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461170B2

Reaction notes

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