Hydrochloric Acid → 4-(Hydroxymethyl)phthalazin-1(2H)-one

Participants

Reaction Steps

With the exclusion of moisture, a solution of 155 ml (1.19 mol) isobutyl chloroformate in 620 ml THF is added dropwise to a suspension of 207 g (1.089 mol) phthalazin-1 (2H)-one-4-carboxylic acid in 6 l THF and 166 ml (1.188 mol) triethylamine at about 10° C. After stirring for 3 h at RT, the mixture is filtered and the residue washed with 0.5 l THF. The yellow filtrate is cooled to 15° C., then 93 g (2.46 mol) sodium borohydride is added and the suspension stirred for about 8 h at RT. To complete the reduction, another 10 g sodium borohydride is added and the mixture heated for 5 h to 40° C. Then 0.5 l water and finally 0.5 l of 5 N HCl are added dropwise at 15° C. and the turbid solution is stirred for 30 min. The reaction mixture is diluted with 3 l EtOAc and 2 l semisaturated brine, the aqueous phase is separated off and extracted 3 times with 2 l EtOAc. The organic phases are washed twice each time with semisaturated brine and brine, dried (Na2SO4) and concentrated by evaporation. Stirring in water at 90° C., cooling and filtration yield the title compound; m.p. 199-201° C.; 1H-NMR (DMSO-d6) 12.52 (s, HN), 8.25 (d, 1H), 8.11 (d, 1H), 7.9 (m, 2H), 5.49 (t, HO), 4.68 (d, 2H); FAB-MS (M+H)+=177.

Provenance & Evidence