Dimethylformamide → 2,2,2-trifluoro-N-(4-formyl-3,5-dimethylphenyl)acetamide

HRID 1360771Notes

Reaction equation

Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[CH3:16].C[Li].[Li+].[Br-].[Li]C(CC)C.CN([CH:29]=[O:30])C>C1COCC1.CCOCC.C1CCCCC1>[F:12][C:11]([F:14])([F:13])[C:10]([NH:9][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([CH:29]=[O:30])=[C:3]([CH3:16])[CH:4]=1)=[O:15]

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of N-(4-bromo-3,5-dimethylphenyl)-2,2,2-trifluoroacetamide (U.S. Pat. No. 6,391,865) (14.0 g. 47.3 mmol) in THF (200 mL) under nitrogen atmosphere at −78° C. was added slowly methyllithium/LiBr (44.1 mL of a 1.5 M solution in Et2O, 66.2 mmol). After 5 min of stirring, sec-BuLi (47.3 mL of a 1.4 M solution in cyclohexane, 66.2 mmol) was added slowly to the reaction solution at −78° C. After 5 min, anhydrous DMF (25.5 mL, 331 mmol) was added slowly then the solution was warmed to 25° C. After 30 min the reaction mixture was quenched with water. The aqueous layer was extracted with CH2Cl2 and the combined organic layers were washed with water, brine, dried over MgSO4 and filtered. The solvent was removed under reduced pressure to give the title compound as a yellow solid. MS: m/z 246 (M+1).

Workup

waitAfter 5 min
customAfter 30 min the reaction mixture was quenched with water
extractionThe aqueous layer was extracted with CH2Cl2
washthe combined organic layers were washed with water, brine
dry with materialdried over MgSO4
filtrationfiltered
customThe solvent was removed under reduced pressure

Sources & evidence

ORD record: ord-2b8037a6960048a58faaa0146acf5adf
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879850B2

Reaction notes

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