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

Temperature

-78 °C

Tert-butyl 2,4-dimethoxybenzylcarbamate (3.96 g, 14.8 mmol) was dissolved in THF (74 mL) and cooled to −78° C. The solution was treated with butyl lithium (7.44 mL, 16.3 mmol) dropwise over a five minute period to afford a pale-yellow solution. The solution was allowed to stir for 15 minutes before the chloro(methoxy)methane (1.35 mL, 17.8 mmol) was added dropwise (neat). The reaction was stirred at −78° C. for 10 minutes, then 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 layer was extracted once, and the organics were combined. The organic layer 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.

1. customto afford a pale-yellow solution
2. additionwas added dropwise (neat)
3. temperatureto warm slowly to ambient temperature overnight
4. concentrationThe reaction was concentrated in vacuo
5. customto afford a yellow gel which
6. customwas partitioned between half-saturated NH4Cl solution and ether
7. extractionThe aqueous layer was extracted once
8. washThe organic layer was washed with water
9. custombrine, separated
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-e3c675e4aeaf445795749a09218329e6

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150548B2