(2-Fluoro-6-methylphenyl)methanol, (6-Fluoro-o-tolyl)methanol synthesis

Yield:-

Reaction Conditions:

Stage #1: 2-fluoro-6-methylbenzoyl chloridewith thionyl chloride in tetrahydrofuran at 0 - 20; for 2.33333 h;
Stage #2: with hydrogenchloride;water in tetrahydrofuran;

Steps:

26.5

To a solution of the acid from Step 4 (3.60 g, 23.4 mmol) in thionyl chloride (40 mL) was added DMF (0.42 mL) and the mixture was heated to reflux for 5.5 h. The mixture was cooled to room temperature and concentrated. The residue was taken up in THF (40 mL) and added over 20 min to a 0 ⁰C slurry of NaBH₄ (3.53 g, 93.4 mmol) in THF (40 mL). The mixture was stirred at room temperature for 2 h and then quenched by the addition of H₂O and 4 M HCI and extracted with EtOAc. The combined organic phase was washed with sat. NaHCO₃ and brine, dried (MgSO₄) and concentrated to afford 2.67 g (~ 75%) of the benzyl alcohol, a pale yellow solid. ¹H NMR (400 MHz, CDCI₃) δ 2.42 (s, 3 H), 4.72 (s, 2 H), 6.88 (t, J=9.0 Hz, 1 H), 6.96 (d, J=7.6 Hz, 1 H), 7.07 - 7.20 (m, 1 H).

References:

WO2006/128142,2006,A2 Location in patent:Page/Page column 51