Methanol → Methyl 3-fluoro-4-(2-hydroxy-2-methyl-propyl)benzoate

Participants

Reaction Conditions

Reaction Steps

1-(4-Bromo-2-fluoro-phenyl)-2-methyl-propan-2-ol (2.35 g, 9.51 mmol), diacetoxypalladium (214 mg, 0.951 mmol), 3-diphenylphosphanylpropyl-diphenyl-phosphane (404 mg, 0.951 mmol), and Et3N (4.24 mL, 30.4 mmol) in DMF (26 mL) were treated with MeOH (20.0 mL, 495 mmol). The vessel was charged to 50 psi with CO (266 mg, 9.51 mmol) and then vented. This operation was repeated twice. The reaction was charged to 50 psi and heated at 80° C. for 15 h. The reaction mixture was allowed to cool, vented and partitioned between EtOAc/brine. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organics were washed twice with brine, dried over Na2SO4, filtered and concentrated to an orange oil. The residue was purified by silica gel flash column chromatography using 0-30% EtOAc in hexanes to yield methyl 3-fluoro-4-(2-hydroxy-2-methyl-propyl)benzoate (1.83 g, 85%) ESI-MS m/z calc. 226.1, found 227.5 (M+1)+; Retention time: 1.29 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.78 (dd, J=7.9, 1.7 Hz, 1H), 7.71 (dd, J=10.3, 1.6 Hz, 1H), 7.34 (t, J=7.6 Hz, 1H), 3.92 (s, 3H), 2.88 (d, J=1.3 Hz, 2H), 1.26 (s, 6H).

Provenance & Evidence