Tetrahydrofuran → 1-(3,4,5-Trimethoxybenzyl)-3-(4-fluorophenylmethyl)-2-oxopyrrolidine

HRID 323495Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]=[C:14]([O:18][CH3:19])[C:15]=1[O:16][CH3:17])[CH2:6][N:7]1[CH2:11][CH2:10][CH2:9][C:8]1=[O:12].O1CCCC1.C([Li])(CC)C.[F:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35]Br)=[CH:33][CH:32]=1>C(OCC)(=O)C.CCCCCC.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]=[C:14]([O:18][CH3:19])[C:15]=1[O:16][CH3:17])[CH2:6][N:7]1[CH2:11][CH2:10][CH:9]([CH2:35][C:34]2[CH:37]=[CH:38][C:31]([F:30])=[CH:32][CH:33]=2)[C:8]1=[O:12]

Participants

Conditions

Temperature: -78 °C

Procedure

Combine 1-(3,4,5-trimethoxybenzyl)-2-oxopyrrolidine (0.98 g, 3.70 mmol) and tetrahydrofuran (10 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of sec-butyl lithium (2.99 mL, 1.3 M in hexane, 3.88 mmol). After 30 minutes, add 4-fluorobenzyl bromide (0.70 g, 3.70 mmol). After the addition is complete, warm to ambient temperature. After 2 hours, add water and extract three times with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with ethyl acetate/hexane 1/1 to give the title compound.

Workup

additionAfter the addition
temperaturewarm to ambient temperature
waitAfter 2 hours
extractionextract three times with ethyl acetate
dry with materialDry the combined organic layers over Na2SO4
filtrationfilter
concentrationconcentrate in vacuo
customto obtain a residue

Sources & evidence

ORD record: ord-683e3a22071b46e29344acca5ed5196c
Source dataset: uspto-grants-2001_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06211199B1

Reaction notes

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