Nitric Acid → 1-(Benzyloxy)-2,3-dimethoxybenzene

Participants

Reaction Steps

from 2-chloro-N-(3-methoxyphenyl)-4-pyrimidineamine (1 62 mg, 0.69 mmol) [see Example 92] and 3-benzyloxy-4,5-dimethoxyaniline (180 mg, 0.69 mmol) to afford the title compound (255 mg) as an off-white solid m.p. 83-84°. δH (CDCl3) 8.01 (1H, d, J 5.8 Hz), 7.45-7.22 (6H, m), 6.95 (3H, m), 6.90 (1H, d, J 7.6 Hz), 6.79 (1H, d, J 2.4 Hz), 6.68 (1H, d, J 7.6 Hz), 6.48 (1H, s), 6.17 (1H, d, J 5.8 Hz), 5.11 (2H, s), 3.86 (3H, s), 3.82 (3H, s) and 3.78 (3H, s). MS m/z 369 (M+H)+. The 3-benzyloxy-4,5-dimethoxyaniline was prepared by heating a solution of 1-benzyloxy-2,3-dimethoxy-5-nitrobenzene (1.80 g, 6.23 mmol) in ethanol (15 ml) with saturated aqueous sodium hydrosulphite (20 ml) at reflux for 2 h. An additional quantity of sodium hydrosulphite (20 ml) was added and reflux continued for a further 4 h. The reaction mixture was reduced to a small volume then diluted with water and extracted three times with ethyl acetate. The organic phase was dried (MgSO4) and evaporated to give the crude product which was recrystallised from etherhexane to give the desired product (356 mg) as a white crystalline solid m.p. 118-120°. MS m/z 260 (M+H)+. The 1-benzyloxy-2,3-dimethoxy-5-nitrobenzene used as starting material was prepared by treating a solution of 1-benzoyl-2,3-dimethoxybenzene (7.25 g, 29.66 mmol) in glacial acetic acid (15 ml) portionwise with 70% nitric acid (2.84 ml) at room temperature. After 2 h, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic phase was washed with 1 M NaOH, then brine, dried (MgSO4) and evaporated. The crude product was purified by column chromatography [silica 20% ethyl acetate-hexane] to give, after recrystallisation from CH2Cl2 -hexane, the desired product (1.89 g) as a white solid m.p. 101-102°. MS m/z (relative intensity) (M+H)+ 289 [(M+H),+ 2%] 91 [100%]. 1-Benzyloxy-2,3-dimethoxybenzene was prepared by the method of F Dietl et al Synthesis, 626 (1985).

Provenance & Evidence