Toluene → HCID 178501098, compound

Participants

Reaction Conditions

Reaction Steps

Cool a suspension of (5S)—N-[3,5-bis(trifluoromethyl)benzyl]-7,9-dimethyl-N-(2-methyl-2H-tetrazol-5-yl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-amine (3.40 g, 6.82 mmol), sodium triacetoxyborohydrate (3.01 g, 13.64 mmol), and ACN (28 mL) to −12° C. to −10° C. in an ice/acetone bath and add a solution of (trans)-4-formylcyclohexanecarboxylate (2.03 g, 11.93 mmol) in toluene (18.5 mL) over 30 min via a syringe pump (0.66 mL/min). Continue stirring the reaction in an ice/acetone bath for 2 hours. Add 44 mL of 10% (by weight) NH4Cl in water to the reaction and stir for 30 min at room temperature. Stop stirring and there are two layers. Separate the layers, concentrate the organic layer down to one volume of solvent. Add 24 mL of ethanol and concentrate to a solid (or to one volume). Add 24 mL of ethanol, 2 mL of water and heat to 60° C. (still a suspension). Add 2 mL of water dropwise. Allow the suspension to cool to room temperature and stir overnight at room temperature. After stirring overnight at room temperature, cool the suspension to −10° C. for 0.5 h, then filter. Wash the filter solids with 3 mL of −10° C. EtOH:water (4:1). Dry the solids overnight in a vacuum oven at 50° C. to give 4.24 g of methyl-trans-4-{[(5S)-5-{[3,5-bis(trifluoromethyl)benzyl](2-methyl-2H-tetrazol-5-yl)amino}-7,9-dimethyl-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]methyl}cyclohexanecarboxylate as a colorless solid. HPLC shows 99.75% pure.

Provenance & Evidence