tert-Butanol → Ethyl 1-[[(1,1-dimethylethoxy)carbonyl]amino]-3,3-difluorocyclobutanecarboxylate

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Reaction Steps

To a solution of 1-(ethoxycarbonyl)-3,3-difluorocyclobutanecarboxylic acid (162) (1 g, 4.8 mmol) in dry dioxane (18 mL) was added tert-butanol (0.4 mL, 4.3 mmol), DPPA (1.03 mL, 4.8 mmol) and TEA (0.7 mL, 4.9 mmol) and the mixture was refluxed overnight. Ethyl acetate was added and the organic layer was washed twice with 5% citric acid and saturated sodium hydrogen carbonate. The solution was dried and evaporated under reduced pressure. The product was purified using silica gel chromatography using hexanes/ethyl acetate to yield ethyl 1-((tert-butoxycarbonyl)amino)-3,3-difluorocyclobutanecarboxylate (163). 1H NMR (400 MHz, CD2Cl2) δ 4.12 (q, J=6.8 Hz, 2H), 3.18-3.08 (m, 2H), 2.73-2.55 (m, 2H), 1.34 (s, 9H), 1.19 (t, J=6.8 Hz, 4H). MS m/z 280.1 (M+1)+.

Provenance & Evidence