Sodium Carbonate → 1-Benzyl-3-(3,4-difluorophenyl)pyrrolidin-3-ol

HRID 1931894Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([F:9])[CH:3]=1.C([Li])CCC.[CH2:15]([N:22]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)C>[CH2:15]([N:22]1[CH2:26][CH2:25][C:24]([C:2]2[CH:7]=[CH:6][C:5]([F:8])=[C:4]([F:9])[CH:3]=2)([OH:27])[CH2:23]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-bromo-3,4-difluorobenzene (5.0 g, 25.9 mmol) in dry diethyl ether (40 mL), under nitrogen, was added dropwise at −78° C., n-butyllithium (2.5 M in hexane, 10.36 mL, 25.9 mmol). The mixture was stirred for 1 h after which a solution of 1-benzylpyrrolidin-3-one (3.63 g, 20.7 mmol) in dry diethyl ether (20 mL) was added drop wise. The resulting mixture was stirred for 1 h at −78° C. and then brought to ambient temperature. Aqueous sodium carbonate (10%, 50 mL) was added and the aqueous phase was extracted with ethyl acetate (3×50 mL). The combined organic phase was washed with brine, dried (MgSO4) and evaporated. Purification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:1) gave the title compound (3.6 g). MS m/z (rel. intensity, 70 eV) 289 (M+, 3), 198 (74), 133 (44), 132 (38), 91 (bp).

Workup

additionwas added drop wise
custombrought to ambient temperature
extractionthe aqueous phase was extracted with ethyl acetate (3×50 mL)
washThe combined organic phase was washed with brine
dry with materialdried (MgSO4)
customevaporated
customPurification by flash column chromatography on silica gel (ethyl acetate/isooctane, 1:1)

Sources & evidence

ORD record: ord-71cf86ae383c4206be371c2275bdce69
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188301B2

Reaction notes

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