Acetyl chloride → 1-(1,1-Dimethylethyl)-2-(methoxymethoxy)benzene

Participants

Reaction Steps

The following reaction was carried out in an efficient fume cupboard. To a solution of 2-tert-butylphenol (322 g, 2.1 moles) dissolved in 1.5 liters of degassed HPLC grade thf (tetrahydrofuran) in a flask fitted with an efficient condenser was added chunks of sodium (52 g, excess) and the reaction mix allowed to react for 3 hours then refluxed overnight to complete the reaction. A solution of MOMCl was formed in a 3 liter, 3 neck flask fitted with an efficient double surfaced condenser, pressure equalizing dropping funnel and a nitrogen inlet in a water bath at RT by the slow addition of AcCl (205 g, 2.6 moles) to dimethoxymethane (229 g, 3.0 moles) with a catalytic amount of ZnCl2 (2 g). Caution MOMCl is a known carcinogen and the reaction is exothermic!! After addition of the AcCl the reaction mixture is stirred for 30 minutes and the dropping funnel replaced with a septum. The thf solution of sodium phenolate added by cannula and the reaction mix stirred for 1 hour to complete the reaction. The reaction mix is deactivated by the addition of 500 mls of 2 M NaOH solution and stirring for a further 60 minutes to decompose excess MOMCl. Ether (500 mls) is added and the phases separated. The organic phase was washed with 3×500 mls of distilled water and dried over MgSO4, filtered and the ether removed on a Rota-Vap. The unreacted phenol was removed by passage through a basic alumina column using hexane as elutriation solvent. The recovered material (compound “5.1”) was purified by flash distillation under reduced pressure, 67-68° C. 0.4 mm Hg. Yield 287 g (74%). 1H-NMR (250 MHz, CDCl3) δ 1.420(s, 9H, C(CH3)3), 3.519(s, 3H, OMe), 5.253(s, 2H, OCH2O), 6.92-7.33(m, 4H, Ar—H).

Provenance & Evidence