Hydrochloric Acid → (7-Chloroquinolin-4-yl)methanol

Participants

Reaction Conditions

Reaction Steps

A 200 ml stainless steel autoclave was loaded with 4-bromo-7-chloroquinoline (1.2 g, 5.0 mmol) (Can. Pat. CA 94-2133620 941004), bis(triphenylphosphine)palladium chloride (0.1 g), triethylamine (3 ml) and ethanol (40 ml) and pressurized to 200 psi with carbon monoxide. The autoclave was heated at 120° C. for 12 hours, cooled, and vented. Solids were removed by filtration through celite and the mother liquor concentrated in vacuo. The residue was taken up in chloroform (50 ml), washed with water (3×50 ml), saturated brine (50 ml), and dried (Na2SO4). Filtration and removal of solvent left 1.3 g of a brown liquid. Flash chromatography on silica using 1 vol % CH3CN in CH2Cl2 as eluent afforded product as a colorless syrup which solidified to a waxy solid. This solid was dissolved in methanol (50 ml) and sodium borohydride was added over two hours until judged complete by TLC. The reaction was diluted with water and acidified with 1N hydrochloric acid and then neutralized with sodium bicarbonate. The resulting solid was recovered via filtration, dissolved in ethyl acetate and dried (MgSO4). Filtration and concentration afforded the desired compound (mp: 160° C., 0.66 g, 68% over two steps).

Provenance & Evidence