Water → 3-((3S,4S)-3-fluoro-4-(4-hydroxy-phenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one

HRID 1507223Notes

Reaction equation

Br[CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[C:3]1=[O:15].C(N(CC)CC)C.Cl.[F:24][C@H:25]1[C@H:30]([C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH2:29][CH2:28][NH:27][CH2:26]1.O>CN(C=O)C>[F:24][C@H:25]1[C@H:30]([C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)[CH2:29][CH2:28][N:27]([CH:2]2[CH2:6][CH2:5][N:4]([CH2:7][C:8]3[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=3)[C:3]2=[O:15])[CH2:26]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 3-bromo-1-(4-methylbenzyl)pyrrolidin-2-one (200 mg, 0.75 mmol), triethylamine (0.52 mL, 3.7 mmol) and 4-((3S,4S)-3-fluoropiperidin-4-yl)phenol hydrochloride (173 mg, 0.75 mmol) in DMF (3 mL) was heated to 120° C. in a microwave reactor for 1.5 h. The mixture was allowed to cool and was then mixed with 60 mL water and extracted 5 times with 40 mL of DCM. The combined organic extracts were washed with 80 mL of brine, dried over anhydrous sodium sulfate, filtered, and evaporated to give 265 mg of 3-((3S,4S)-3-fluoro-4-(4-hydroxy-phenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one as a mixture of 2 diastereoisomers. LCMS (method P) RT 0.92 min m/z 383.4 (M+H+).

Workup

temperatureto cool
extractionextracted 5 times with 40 mL of DCM
washThe combined organic extracts were washed with 80 mL of brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-cc4e422416b94d3b94092ee336d24a1a
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221796B2

Reaction notes

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