Chloromethyl Methyl Ether → Tert-butyl 2,4-dimethoxybenzyl(methoxymethyl)carbamate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 2,4-dimethoxybenzylcarbamate (3.96 g, 14.8 mmol) was dissolved in THF (74 mL) and cooled to −78° C. Butyl lithium (7.44 mL, 16.3 mmol) was added dropwise to the solution over a five minute period to afford a pale-yellow solution. The solution was allowed to stir for 15 minutes before chloro(methoxy)methane (1.35 mL, 17.8 mmol) was added dropwise (neat). The reaction was stirred at −78° for 10 minutes and allowed to warm slowly to ambient temperature overnight. The reaction was concentrated in vacuo to afford a yellow gel, which was partitioned between half-saturated NH4Cl solution and ether. The aqueous portion was extracted once, and the organics were combined. The organic portion was washed with water, then brine, separated, dried over Na2SO4, filtered, and concentrated in vacuo. 1H NMR supports the desired near-pure (>90%) tert-butyl 2,4-dimethoxybenzyl(methoxymethyl)carbamate (4.81 g, 104% yield) as a pale-yellow oil which was used without purification.

Provenance & Evidence