Dimethylformamide → 2-Chloro-6-fluoro-3-(phenylmethoxy)benzaldehyde

HRID 250635Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[Cl:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:24]=[O:25]>O1CCCC1>[CH2:1]([O:8][C:9]1[C:10]([Cl:16])=[C:11]([C:12]([F:15])=[CH:13][CH:14]=1)[CH:24]=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-benzyloxy-2-chloro-4-fluoro-benzene (618, 5.8 g, 0.024 mol) in tetrahydrofuran (100 mL) was added 2.50 M of n-butyllithium (2.7 mL, 2.50 M in hexane, 0.029 mol) slowly at −78° C. over 15 minutes under nitrogen. The reaction mixture was stirred at −78° C. for 30 minutes. To the reaction mixture was then added N,N-dimethylformamide (4.2 mL, 0.054 mol). The reaction was allowed to warm to room temperature and was continued at room temperature overnight. The reaction mixture was poured into ice water, extracted with ethyl acetate, washed with hydrochloric acid (10%), water, brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexane to provide the compound as a white solid (619, 2.1 g, 32%). MS (ESI) [M+H+]+=265.08.

Workup

temperatureto warm to room temperature
waitwas continued at room temperature overnight
extractionextracted with ethyl acetate
washwashed with hydrochloric acid (10%), water, brine
dry with materialdried over magnesium sulfate
customAfter removal of solvent
customthe residue was purified by silica gel column chromatography
washeluting with ethyl acetate in hexane

Sources & evidence

ORD record: ord-08299653d13b4140862e4758603a9a85
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863288B2

Reaction notes

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