Potassium Carbonate → (R)-3-(4-Fluorophenoxy)butanoic acid

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C@H:7]([CH3:12])[CH2:6][C:5]2=[O:13].Cl.NO.C([O-])([O-])=[O:18].[K+].[K+]>O>[F:1][C:2]1[CH:11]=[CH:10][C:9]([O:8][C@H:7]([CH3:12])[CH2:6][C:5]([OH:13])=[O:18])=[CH:4][CH:3]=1

Participants

Procedure

6-fluoro-2,3-dihydro-2-methylchromen-4-oxime (13). To a suspension of the ketone 12 (2.79 g, 15.5 mmol) was added a solution of hydroxylamine hydrochloride (2.09 g, 30 mmol) and K2CO3 (1.2 g, 8.75 mmol) in 18 mL of H2O. The reaction mixture was refluxed for four hours. After cooling to room temperature, the solution was removed under vacuum, and the residual solid was triturated with ice water. The crude product was recrystallized from EtOH to give 3.2 g (84%) of the white solid oxime 13, m.p. 102-105° C., 1H NMR (CDCl3) δ 7.58 (br s, 1H), 7.48 (dd, J=3.0, 9.5 Hz, 1H), 6.97 (ddd, J=3.0, 9.0, 8.0 Hz, 1H), 6.85 (dd, J=4.5, 9.0 Hz, 1H), 4.21-4.15 (m, 1H), 3.28 (dd, J=3.0, 17.0 Hz, 1H), 2.37 (dd, J=12.0, 17.0 Hz, 1H), 1.47 (d, J=6.5 Hz, 3H). EI-MS (m/z) 195 (M+). The reaction is shown as follows: