Methanol → (S)-2-(4-Fluorophenyl)-3-methylbutyric acid
Reaction equation
O=O.[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[C:14]([CH3:16])[CH3:15])[C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1.CO>O1CCCC1.[Rh]>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C@H:10]([CH:14]([CH3:16])[CH3:15])[C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1Participants
Procedure
Rhodium-catalyzed hydrogenation. -- A catalyst solution was prepared in a glove box (O2 content <1 ppm) by dissolving 0.01045 g (0.0257 mmol) of [Rh(COD)2 ]BF4 and 0.01861 g (0.0257 mmol) of (R,S)-BPPFA-EPIP in 20 ml of tetrahydrofuran and stirring at RT for 15 minutes. Then, 5.0 g (25.75 mmol) of 2-(p-fluorophenyl)-3-methylcrotonic acid, 13 ml of methanol and 33 ml of tetrahydrofuran were placed in a 185 ml autoclave and the catalyst solution prepared above was added. The autoclave was sealed and the hydrogenation was carried out at 20° while stirring and under a constant pressure of 50 bar. The conversion was 100% after 24 hours. The hydrogenation solution was evaporated at 50°/200 mbar and the residue was distilled at 108-110°/0.01 mbar. There were obtained 4.8 g (97%) of (S)-2-(p-fluorophenyl)-3-methylbutyric acid as a colorless oil which solidified at RT; 98.2% ee.
Workup
- customthe catalyst solution prepared
- additionabove was added
- customThe autoclave was sealed
- customwas carried out at 20°
- stirringwhile stirring and under a constant pressure of 50 bar
- customafter 24 hours
- customThe hydrogenation solution was evaporated at 50°/200 mbar
- distillationthe residue was distilled at 108-110°/0.01 mbar
Sources & evidence
- ORD record
- ord-2feadb2cb5ae4dd7842c92540b1568ae
- Source dataset
- uspto-grants-1999_06
- Patent number
- US05910606
Reaction notes
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