Ammonia → (1S,2R,4S,5R)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylate

Participants

Reaction Steps

To a vial containing (1R,2S,5S)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,5R)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylate (0.305 g, 1.67 mmol) was added a solution of ammonia (2 Nin EtOH) followed by titanium(IV) isopropoxide (0.54 mL, 1.8 mmol). The vial was capped and the reaction was stirred at room temperature overnight. Sodium borohydride (0.095 g, 2.5 mmol) was added and reaction mixture was stirred for about 5 h. Concentrated NH4OH (5 mL) was added and the resulting mixture was stirred for about 5 min. The resulting suspension was filtered and the filter cake was washed with EtOAc (60 mL). The filtrate was partitioned and the aqueous layer was extracted with EtOAc (30 mL). The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated to yield (1R,2S,4R,5S)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,4S,5R)-ethyl 4-amino-1-methylbicyclo[3.1.0]hexane-2-carboxylate (0.21 g, 69%). This amine (0.212 g, 1.16 mmol) was reacted with cyclopropanesulfonyl chloride (0.244 g, 1.74 mmol) using General Procedure N to give (1R,2S,4R,5S)-ethyl 4-(cyclopropanesulfonamido)-1-methylbicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,4S,5R)-ethyl 4-(cyclopropanesulfonamido)-1-methylbicyclo[3.1.0]hexane-2-carboxylate (0.11 g, 33%): LC/MS (Table 2, Method a) Rt=2.06 min; MS m/z: 286 (M−H)−.

Provenance & Evidence