Potassium Carbonate → (S)-tert-butyl 4-(3-(4-bromo-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407879Notes

Reaction equation

CS([O:5][C@@H:6]1[CH2:10][CH2:9][N:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[C:7]1=[O:24])(=O)=O.[Br:25][C:26]1[CH:31]=[CH:30][C:29](O)=[C:28]([F:33])[CH:27]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[Br:25][C:26]1[CH:31]=[CH:30][C:29]([O:5][C@H:6]2[CH2:10][CH2:9][N:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[C:7]2=[O:24])=[C:28]([F:33])[CH:27]=1

Participants

Conditions

Temperature: 70 °C

Procedure

(R)-tert-Butyl 4-(3-(methylsulfonyloxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (Preparation D; 1.7 g, 4.7 mmol) was dissolved in dry DMSO (30 mL) and 4-bromo-2-fluorophenol (1.1 g, 5.6 mmol) and K2CO3 (0.78 g, 5.6 mmol) was added and the reaction heated to 70° C. under nitrogen. The reaction became purple then black. The reaction was cooled to ambient temperature after 3 hours and partitioned between water and EtOAc, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (40% EtOAc in hexanes) to afford (S)-tert-butyl 4-(3-(4-bromo-2-fluorophenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (1.8 g, 3.9 mmol, 84% yield) as a white solid.

Workup

temperatureThe reaction was cooled to ambient temperature after 3 hours
custompartitioned between water and EtOAc
extractionextracted with EtOAc
washwashed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified over silica gel (40% EtOAc in hexanes)

Sources & evidence

ORD record: ord-7f141bf48955487790f07a31bf7c3e3f
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754226B2

Reaction notes

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