Dimethylformamide → Isopropyl 3,5-difluoro-4-formylphenylcarbamate

HRID 1179479Notes

Reaction equation

C([Li])CCC.[F:6][C:7]1[CH:8]=[C:9]([NH:14][C:15](=[O:20])[O:16][CH:17]([CH3:19])[CH3:18])[CH:10]=[C:11]([F:13])[CH:12]=1.CN(CCN(C)C)C.CN(C)[CH:31]=[O:32]>C1COCC1>[F:6][C:7]1[CH:8]=[C:9]([NH:14][C:15](=[O:20])[O:16][CH:17]([CH3:18])[CH3:19])[CH:10]=[C:11]([F:13])[C:12]=1[CH:31]=[O:32]

Participants

Conditions

Temperature: -20 °C

Procedure

n-Butyllithium (2.5M in hexane, 112 mL, 0.279 mol) was added dropwise at −78° C. to a solution of isopropyl 3,5-difluoro-phenylcarbamate (20 g, 0.093 mol) and N,N,N,N-tetramethylethylenediamine (32 mL, 0.214 mol) in 93 mL of THF, and stirred for 30 min. Dimethylformamide (10.8 mL, 0.140 mol) was then added dropwise at −78° C., stirred for 1 h, and allowed to warm to −20° C. The reaction was then quenched with saturated aqueous ammonium chloride (100 mL). The reaction mixture was extracted with ethyl acetate, the extracts washed with brine, dried (MgSO4), and concentrated. The crude product was triturated with hexane to provide the title compound. The combined hexane washings were concentrated and purified by flash column chromatography (30% ethyl acetate/hexane) to provide additional product.

Workup

stirringstirred for 1 h
customThe reaction was then quenched with saturated aqueous ammonium chloride (100 mL)
extractionThe reaction mixture was extracted with ethyl acetate
washthe extracts washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated
customThe crude product was triturated with hexane

Sources & evidence

ORD record: ord-3045476fa7ab4bdb901c364235bc4af1
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07279494B2

Reaction notes

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