Dimethylformamide → N-(2-Fluoro-6-formylphenyl)pivalamide

HRID 1172360Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12].C([Li])CCC.C1CCCCC1.CN(C)[CH:29]=[O:30]>O1CCCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH:29]=[O:30])[C:3]=1[NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: -78 °C

Procedure

N-(2-Bromo-6-fluorophenyl)pivalamide (25.5 mmol, 7.0 g) was dissolved in tetrahydrofuran (200 mL). Mixture was cooled to −78° C. 2M Butyllithium in cyclohexane (62.0 mmol, 31.0 mL) was added to the mixture drop-wise. Reaction mixture was held at −78° C. for 30 minutes. A solution of N,N-dimethylformamide (129 mmol, 10.0 mL) in tetrahydrofuran (30 mL) was added to the reaction mixture drop-wise. Reaction was held at −78° C. for 30 minutes. Reaction was quenched with aqueous ammonium chloride then the mixture was allowed to warm to room temperature. Mixture was extracted 2× ethyl acetate. Combined organic layers were dried (magnesium sulfate), filtered and concentrated. Silica gel chromatography afforded the desired product as white solid in 80% yield. 1H NMR (300 MHz, CDCl3): δ=9.93 (d, J=1.83, 1H), 9.14 (bs, 1H), 7.56-7.50 (m, 1H), 7.42-7.25 (m, 2H), 1.34 (s, 9H). MS m/e (M+H)+=224.2.

Workup

customReaction mixture
customReaction
waitwas held at −78° C. for 30 minutes
customReaction
customwas quenched with aqueous ammonium chloride
temperatureto warm to room temperature
extractionMixture was extracted 2× ethyl acetate
dry with materialCombined organic layers were dried (magnesium sulfate)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-acaf17d204424d70bb9b6c28706d036b
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07834007B2

Reaction notes

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