Sodium borohydride → HCID 178479780, compound

Participants

Reaction Conditions

Reaction Steps

A 6.0 mL of the (5,2′-dichloro-biphenyl-2-yloxy)-acetaldehyde stock solution (1.88 mmol) is added to a stirred mixture of 1-hydroxy-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide sodium chloride (438 mg, 1.34 mmol) and 4 Å molecular sieve (400 mg) in anhydrous CH3OH (8 mL) at ambient temperature under nitrogen. The resultant mixture is stirred for 16 hours. After being cooled to 0° C., the mixture is treated with powdered sodium borohydride (112 mg, 2.95 mmol), then stirred at 0° C. for 1 hour and at ambient temperature for another 1 hour. After filtration and subsequent concentration in vacuo, the crude product is chromatographed on silica (gradient 5-15% CH3OH in EtOAc) to give the desired product as a gum. It is dissolved in EtOAc (15 mL), filtered and concentrated to give 493 mg (0.926 mmol, 69% yield) of the free amine as a white solid. The free amine is dissolved in EtOAc (3,0 mL) and subsequently treated dropwise with 1N HCl/Et2O (8 mL) to give a white suspension. After filtration and vacuum drying at 50° C., 470 mg (0.8.26 mmol, 89% yield) of the title compound is obtained as a white powder. ESIMS: m/z 532 [(M+H)+, 35Cl, 35Cl], 534 [(M+H)+, 35Cl, 37Cl], 536 [(M+H)+, 37Cl, 37Cl].

Provenance & Evidence