1,2-Dibromoethane → 1-(4-Cyano-3-fluoro-phenyl)-cyclopropanecarboxylic acid methyl ester
Reaction equation
[H-].[Na+].Br[CH2:4][CH2:5]Br.[CH3:7][O:8][C:9](=[O:20])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[C:13]([F:19])[CH:12]=1>O1CCCC1>[CH3:7][O:8][C:9]([C:10]1([C:11]2[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[C:13]([F:19])[CH:12]=2)[CH2:5][CH2:4]1)=[O:20]Participants
Conditions
- Temperature
- 75 °C
Procedure
Sodium hydride (60% dispersion in mineral oil, 0.360 g) was suspended in anhydrous tetrahydrofuran (60 mL) under nitrogen. 1,2-Dibromoethane (2.0 mL) was added to the suspension, followed by (4-cyano-3-fluoro-phenyl)-acetic acid methyl ester (0.499 g). After the rate of gas evolution slowed, the reaction mixture was transferred to an oil bath and heated to 75° C. for 15 min. The reaction mixture was allowed to cool to ambient temperature and quenched with excess saturated ammonium chloride. The organic layer was separated and the remaining aqueous layer extracted with ethyl acetate (5×60 mL). The combined organics were dried with magnesium sulfate, filtered, and concentrated in vacuo. The crude product (0.637 g) was purified by silica gel chromatography (ethyl acetate:hexanes=2:3) yielding the title compound (0.500 g).
Workup
- customthe reaction mixture was transferred to an oil bath
- temperatureto cool to ambient temperature
- customquenched with excess saturated ammonium chloride
- customThe organic layer was separated
- extractionthe remaining aqueous layer extracted with ethyl acetate (5×60 mL)
- dry with materialThe combined organics were dried with magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product (0.637 g) was purified by silica gel chromatography (ethyl acetate:hexanes=2:3)
Sources & evidence
- ORD record
- ord-386e510986b34d9db9ecd379dc1b43b6
- Source dataset
- uspto-grants-2007_07
- Patent number
- US07250518B2
Reaction notes
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