Application of 4-fluoro-3-methoxybenzyl alcohol_Industrial additives

Background and overview^[1]

4-Fluoro-3-methoxybenzyl alcohol can be used as a pharmaceutical synthesis intermediate. If you inhale 4-fluoro-3-methoxybenzyl alcohol, please move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical treatment if you feel uncomfortable; If eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation ^[1]

4-Fluoro-3-methoxybenzyl alcohol was prepared by adding 4-fluoro-3-methoxybenzaldehyde (1.54 g, 10.0 mmol) in borane in tetrahydrofuran (30 mL) under ice cooling. Tetrahydrofuran complex solution (11.0 mmol was added dropwise to 11.1 ml), and the mixture was stirred at room temperature overnight. Methanol was added, and the solvent was distilled off to obtain (4-fluoro-3-methoxyphenyl)methanol crystals (1.56 g, quantitative). Melting point 47-50℃; ¹ H HNMR (DMSO-d 6) δ: 3.82 (3H, S), 4.45 (2H, S), 5.22 (1H, S), 6.83-6.88 (1 H, m), 7.08-7.16 (2 H, m).

Apply^[1]

4-Fluoro-3-methoxybenzyl alcohol can be used as a pharmaceutical synthesis intermediate. For example, to prepare 4-fluoro-3-methoxyphenyl)acetonitrile, the specific steps are as follows: under ice cooling, add 4-fluoro-3-methoxybenzyl alcohol (1.56 g, 10.0 mmol), acetone cyanohydrin (1.89 g, 20.0 mmol), a suspension of a toluene solution of diethyl azodicarboxylate (5.45 ml, 12.0 mmol) in toluene (40 mL), triphenylphosphine (3.41 g, 13.0 mmol) was added dropwise, Stir at 0°C for 45 minutes and at room temperature overnight. The solvent was evaporated and purified by silica gel column chromatography to give crystals of (4-fluoro-3-methoxyphenyl)acetonitrile (1.11 g, 67%) as an oil. ¹ H NMR (CDCl ₃) δ: 3.72 (2H, S), 3.91 (3H, S), 6.81-6.87 (1H, M), 6.92 (1H , DD, J = 2.0Hz, 7.9Hz), 7.04-7.11 (1H, m).

Main reference materials

[1] WO/2009/072581 LACTAM COMPOUND OR SALT THEREOF, AND PPAR ACTIVATOR