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

HRID 1947822Notes

Reaction equation

C([O:3][P:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)(=[O:8])[O:5]CC)C.Cl>O>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][P:4](=[O:3])([OH:5])[OH:8])=[CH:11][CH:12]=1)([O-:18])=[O:17]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of diethyl(4-nitrobenzyl)phosphonate (I, 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%).

Workup

customthe suspended solid isolated by filtration
washwashed with water
customdried in vacuo

Sources & evidence

ORD record: ord-43483365ffd547868166c5d2c8f67b1a
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399433B2

Reaction notes

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