Cyclopropanecarboxaldehyde → HCID 11283992, compound

Participants

Reaction Steps

To a solution of 0.045 g of 4′-{4-[5,6-dichloro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-benzoimidazol-2-yloxymethyl]-piperidin-4-yl}-biphenyl-3-carbonitrile 55 (0.073 mmol, 1 eq) in 0.5 mL of 1,2-dichloroethane at room temperature was added 6.6 μL of cyclopropanecarboxaldehyde (0.088 mmol, 1.2 eq) and acetic acid (0.005 mL, 1% v/v). The mixture was stirred at room temperature for 1 h followed by the addition of 0.023 g of NaBH(OAc)3 (0.105 mmol, 1.5 eq). The reaction was stirred at room temperature for 16 h and then the solvent was removed by rotary evaporation to yield 0.052 g of the crude product. This intermediate was dissolved in 2 mL of tetrahydrofuran and tetrabutylammonium fluoride on silica gel (1.0-1.5 mmol/g, 0.16 g, 2 eq) was added. The mixture was heated to 60° C. for 16 h then filtered and the resin washed with 10 mL of tetrahydrofuran. The filtrate was concentrated by rotary evaporation and the crude product was purified by flash silica gel chromatography eluting with 1% methanol in dichloromethane with 3% triethylamine to give 0.007 g of the desired product 4′-[1-cyclopropylmethyl-4-(5,6-dichloro-1H-benzoimidazol-2-yloxymethyl)-piperidin-4-yl]-biphenyl-3-carbonitrile 57 MS (ESI): Calcd m/z for C30H28Cl2N4O.H+=531.2. Found m/z 530.9/532.9 [(M+1)+/(M+3)+].

Provenance & Evidence