N-Hydroxyacetamidine → tert-butyl (1R,5R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylate

Participants

Reaction Steps

2-Methyl-tetrahydrofuran (40 mL), acetamide oxime (0.93 g, 0.0125 mol) and sodium methoxide (1.1 g, 0.020 mol) were added to (1R,5R)-3-tert-butyl 1-ethyl 3-azabicyclo[3.1.0]hexane-1,3-dicarboxylate (142) (1.27 g, 0.0050 mol) and the mixture was heated to reflux for 3 hours. Upon cooling the suspension was partitioned between ethyl acetate (100 mL) and water (25 mL). The organic layer was washed with water (25 mL), saturated sodium chloride (25 mL) and dried over Na2SO4. The mixture was concentrated and the residue was chromatographed over 25 g of silica gel with 15-25% ethyl acetate/hexanes, to obtain 0.75 g of clear colorless oil. MS (ESI) m/z 304 [M+K]+. 1H NMR (CDCl3) δ 1.16-1.17 (m, 1H), 1.46 (s, 9H), 1.60 (s, 1H), 1.72-1.75 (m, 1H), 2.36 (s, 3H), 3.49-3.51 (m, 1H), 3.65-3.79 (dd, 1H), 3.91-4.00 (m, 2H).

Provenance & Evidence