Sodium Hydroxide → HCID 44537934, compound

Participants

Reaction Conditions

Reaction Steps

To a 500 mL flask equipped with an internal temperature probe and a mechanical stirrer were added 50 g of (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethyl benzoate diphosphate (from Example 8), 72 mL of tetrahydrofuran and 90 mL of 2 N sodium hydroxide. The resulting mixture was warmed to 38-42° C. and held for 24 hours. Upon disappearance of starting material the tetrahydrofuran was removed by rotary evaporation. The resulting mixture was extracted with 200 ml of isopropyl acetate and washed with water (2×135 mL). The organic layer was concentrated and the residue was azeotropically dried by repeated rotary evaporation with isopropyl acetate. Crude product of (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethanol was isolated as a foamy solid (6.5 g, 99% yield). Crude (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethanol (2.0 g, 5.5 mmol) was combined with 55 mL of a 0.1 M solution of 2,5-dihydroxybenzoic acid in ethanol. The mixture was gently heated to ˜50° C. with stirring to give a solution. The solution was cooled to ˜22° C. and the slurry was stirred for 2 hours and the solid was isolated by filtration. Approximately 2.15 g of the (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethanol 2,5-dihydroxybenzoic acid salt was obtained as a solid (80% yield).

Provenance & Evidence