Methyl trifluoromethyl ketone → Benzyl 1-methyl-6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate

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Reaction Conditions

Reaction Steps

A 0.004 M aqueous solution of EDTA disodium salt dihydrate (354 mL, 0.142 mmol) and 1,1,1-trifluoroacetone (49.6 mL, 567 mmol) was added sequentially to a solution of benzyl 3-methyl-2,5-dihydro-1H-pyrrole-1-carboxylate (15.4 g, 70.9 mmol) in acetonitrile (700 mL) at 0° C. A mixture of oxone (153 g, 248 mmol) and sodium bicarbonate (35.7 g, 425 mmol) was added in 5 portions over 1 h. After additions were complete, the mixture was stirred for another hour at 0° C. and filtered. The filtrate was extracted with dichloromethane (3×300 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 10-40% ethyl acetate in hexanes, gave benzyl 1-methyl-6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (12.5 g, 76% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.73-7.30 (m, 5H), 5.21-4.94 (m, 2H), 4.33-4.05 (m, 1H), 3.93-3.70 (m, 2H), 3.56-3.13 (m, 2H), 1.58-1.44 (m, 3H).

Provenance & Evidence