Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate → Benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a suspension of CuI (0.3 equiv.) in anhydrous THF (0.1M) was added methyl magnesium bromide (3M solution in Et2O, 10 equiv.) at −40° C. The reaction was stirred for 30 min, followed by addition of benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate (1.0 equiv.) in THF (0.1M) at −40° C. Allowed the reaction to warm to 10° C. over 5 h, then quenched with water and extracted with ethyl acetate. The organic phase was concentrated under vacuo and purified via silica gel column chromatography eluting with ethyl acetate and hexanes (50% to 100% ethyl acetate) to yield benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate in 35% yield. LCMS (m/z): 385.0 (MH+), Rt=3.38 min.

Provenance & Evidence