Dimethylformamide → 2-(4-Bromo-2-fluorophenyl)-2-methylpropanenitrile
Reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]#N)=[C:6]([F:13])[CH:5]=1.I[CH3:15].C[N:17]([CH:19]=O)C>C1COCC1.CCOC(C)=O>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:15])([CH3:11])[C:19]#[N:17])=[C:6]([F:13])[CH:5]=1Participants
Procedure
To a slurry of sodium hydride (60% dispersion in mineral oil, 0.82 g, 20.6 mmol) in DMF (20 mL) cooled to 0° C. was added a solution of (4-bromo-2-fluoro-phenyl)-acetonitrile (2.0 g, 9.35 mmol) from Step 1 above, dissolved in THF (10 mL). The reaction was stirred till gas evolution ceased, and then iodomethane (1.3 mL, 20.6 mmol) was added slowly. The reaction was stirred for 30 minutes, and then diluted with 100 mL EtOAc. The solids were removed by filtration, and the organic layer was washed with 100 mL water. The organic layer was dried over MgSO4, and then filtered. The mother liquor was concentrated by rotary evaporation, and the product was distilled under high vacuum (0.3 torr, 45° C.). Yield: 2.25 g, 99%. %. 1H NMR (CDCl3) δ: 2.81 (s, 3H), 2.88 (s, 3H), 7.20-7.25 (m, 3H).
Workup
- stirringThe reaction was stirred for 30 minutes
- customThe solids were removed by filtration
- washthe organic layer was washed with 100 mL water
- dry with materialThe organic layer was dried over MgSO4
- filtrationfiltered
- concentrationThe mother liquor was concentrated by rotary evaporation
- distillationthe product was distilled under high vacuum (0.3 torr, 45° C.)
Sources & evidence
- ORD record
- ord-b5ec935b9fc44632aafeba7530803dca
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08268835B2
Reaction notes
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