Sodium cyanoborohydride → 1'-[3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl(methylamino))-butyl]-spiro(1H-indene-1,4'-piperidine)

Participants

Reaction Steps

To a solution of 3.46 g (10 mmol) of 3-(S)-(3,4-dichlorophenyl)-4-(t-butoxycarbonyl-methylamino)butanal (Example 1) in 20 mL of methanol were added 3.11 g (14 mmol) of spiro(1H-indene-1,4'-piperidine) hydrochloride and 3 g of powdered 4 Å molecular sieves. After 15 min a solution of 2.52 g (40 mmol) of NaCNBH3 in 30 mL of THF was dropwise added. Some gas evolution was observed. After stirring the reaction overnight, the mixture was filtered through a pad of celite, the reaction flask and the pad were rinsed with methanol. The filtrate was concentrated to approximately 10 ml and the residue was partitioned between saturated NaHCO3 and Et2O:EtOAC. The organic layer was washed with water, brine and dried over NA2SO4. The filtrate was concentrated and the residue was chromatographed on a flash column using a gradient of 49:49:2 to 98:0:2 EtOAc: Hexane: triethylamine to furnish 4.05 g (79%) of the title compound as a foam.

Provenance & Evidence