Disodium Hydrogen Citrate → HCID 130272602, compound

Participants

Reaction Steps

To a solution of (1S,3S,5R,6S)-ethyl 3-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylate (WO 2000/37410 pamphlet, 37.17 g) in 8 mol/L ammonia-methanol (250 mL), tetraisopropyl orthotitanate (68.09 g) and trimethylsilyl cyanide (23.03 g) were added dropwise sequentially while cooling on ice. The mixture was stirred on ice for 3.5 hours and then a 12.4% aqueous disodium citrate solution (848 g) was added dropwise to the reaction solution. The mixture was extracted twice with toluene (743 ml) and then the combined organic layer was dried over anhydrous sodium sulfate. The insoluble was collected by filtration and then washed with toluene (186 mL), and the solution containing (1S,2S,3S,5R,6S)-ethyl 2-amino-2-cyano-3-fluorobicyclo[3.1.0]hexane-6-carboxylate (Reference Example 2-1) was used for the next reaction without concentration and purification of the filtrate.

Provenance & Evidence