o-Xylyl bromide → Methyl 3-hydroxy-5-{[(2-methylphenyl)methyl]oxy}benzoate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 3,5-dihydroxybenzoate (50 g, 0.30M) in N,N-dimethylformamide (500 ml) at 0° C. was added sodium hydride (10.8 g, 0.27M) portionwise, maintaining the reaction temperature below 10° C. The reaction was allowed to warm to 15° C. and was stirred for 20 minutes. The mixture was cooled to 0° C. and a solution of 2-methylbenzyl bromide (36 ml, 0.27M) in N,N-dimethylformamide (50 ml) was added over 30 minutes. The reaction was warmed to ambient temperature and concentrated ‘in vacuo’. Ethyl acetate (500 ml) was added to the residue and the resulting organic solution was washed first with water (2×250 ml) and then with a saturated aqueous sodium chloride solution (200 ml). The organic layer was dried with magnesium sulfate and then concentrated ‘in vacuo’. The crude product was chromatographed on Kieselgel 60, eluting with a gradient of 0–100% ethyl acetate in iso-hexane to give methyl 3-hydroxy-5-(2-methylbenzyloxy)-benzoate as a colourless solid (21.9 g); H1 NMR δ (d6-DMSO) 2.39 (3H s) 3.90 (3H s) 5.02 (2H s) 5.61 (1H s) 6.69 (1H t) 7.15–7.42 (6H, m). MS [MH]+ 488

Provenance & Evidence