Hydrochloric Acid → (4-Nitro-benzyl)-phosphonic acid

Participants

Reaction Conditions

Reaction Steps

A mixture of diethyl (4-nitrobenzyl)phosphonate (1,700 mg, 2.56 mmol) and 5 mL concentrated HCl was heated at 120° C. for 6 hours. The cooled mixture was then diluted with water, the suspended solid isolated by filtration, washed with water and dried in vacuo to afford 500 mg of (4-nitrobenzyl)phosphonic acid (II) which was used without further purification. This material was mixed with oxalyl chloride (5 mL) and heated at 65° C. under nitrogen for 12 hr after which time the mixture was concentrated in vacuo to afford crude (4-nitrobenzyl)phosphonic dichloride (III). This dichloride was dissolved in dry methylene chloride (5 mL), cooled in ice under nitrogen and treated with n-butanol (1.05 mL, 11.5 mmol) and DIPEA (0.88 mL, 5.07 mmol). After 1 hr at room temperature the mixture was concentrated in vacuo and chromatographed over silica gel eluting with EtOAc:hexane 30-70% to yield 498 mg of dibutyl (4-nitrobenzyl)phosphonate (IV, R=nBu) yield: 66%). A solution of this phosphonate ester in methanol (5 mL) was hydrogenated in the presence of 5% Pd/C (32 mg) for 2 h The suspension was filtered and the filtrate concentrated in vacuo to afford 368 mg of dibutyl (4-aminobenzyl)phosphonate (yield: 82%).

Provenance & Evidence