2-Fluoro-5-nitrobenzaldehyde → (2-Fluoro-5-nitrophenyl)methanol

Participants

Reaction Conditions

Reaction Steps

Sodium borohydride (15.0 g, 0.397 mol) was added portionwise to a 0° C. solution of 2-fluoro-5-nitrobenzaldehyde (82.4 g, 0.487 mol) in anhydrous methanol (1 L). The reaction mixture was stirred at 0° C. for 0.5 hours and was quenched by adding 1N hydrochloric acid solution (500 mL), which resulted in a pH range of between 4 and 5. The product, which precipitated out when methanol was removed, was collected by filtration. To obtain additional product, the filtrate was extracted with ether (4×500 mL). The ether layer was washed with brine and dried to give crude material which was combined with the other material and recrystallized from ethyl acetate in petroleum ether to give 1-fluoro-2-hydroxymethyl-4-nitrobenzene (69.4 g, 0.406 mol, 83%, mp 50°-53° C.). This material was dissolved in ethyl acetate (1 L) and treated with stannous chloride dihydrate (451 g, 1.99 mol) at reflux temperature for 24 hours. The reaction mixture was poured into ice water (1.5 L), basified using 2.5N sodium hydroxide solution to pH 9, and extracted with ethyl acetate (4×1 L), which was washed with brine and dried. Removal of ethyl acetate gave 3-hydroxymethyl-4-fluoroaniline (34.2 g, 60%, mp 80°-84° C.; Tani et al., Chem. Pharm. Bull. 30, 3530, 1982: mp 95°-98° C.).

Provenance & Evidence