Diisopropylamine → 2-(4-Cyano-3-fluorophenyl)acetic acid
Reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CN(P(N(C)C)(N(C)C)=[O:17])C.[F:24][C:25]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:26]=1[C:27]#[N:28].C1[CH2:38][O:37]CC1>>[C:27]([C:26]1[CH:29]=[CH:30][C:31]([CH2:33][C:38]([OH:37])=[O:17])=[CH:32][C:25]=1[F:24])#[N:28]Participants
Procedure
A solution of dry diisopropylamine (16.5 g, 163 mmol) in dry THF (150 mL) under nitrogen was cooled with a −78° C. dry ice/acetone bath, and n-butyl lithium (2.50 M in hexane, 65.2 mL) was added slowly. The resulting solution was warmed to ambient temperature for 10 min and then cooled to −78° C. again. HMPA (30.0 mL, 168 mmol) was added, followed by a solution of 2-fluoro-4-methylbenzonitrile (20.0 g, 148 mmol) in 50 mL of dry THF. After stirring at −78° C. for 2 hours, CO2 was bubbled through the solution for 20 min, and then the mixture was warmed slowly to 0° C. Then 1 N HCl was added until pH=2 and the mixture was extracted with EtOAc. The organic layers were washed with brine and dried over anhydrous sodium sulphate and concentrated to afford (4-cyano-3-fluorophenyl)acetic acid.
Workup
- temperaturecooled to −78° C. again
- customCO2 was bubbled through the solution for 20 min
- temperaturethe mixture was warmed slowly to 0° C
- additionThen 1 N HCl was added until pH=2
- extractionthe mixture was extracted with EtOAc
- washThe organic layers were washed with brine
- dry with materialdried over anhydrous sodium sulphate
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-c99249b914de409fabd3b0f532524c81
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673920B2
Reaction notes
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