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

HRID 2119302Notes

Reaction equation

HRID 2119302 reaction equation
ClC(OCC(C)C)=O.[C:9]1(=[O:22])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([C:19](O)=[O:20])=[N:11][NH:10]1.C(N(CC)CC)C.[BH4-].[Na+].Cl>C1COCC1.CCOC(C)=O.[Cl-].[Na+].O.O>[OH:20][CH2:19][C:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9](=[O:22])[NH:10][N:11]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 7768554-Oxo-3,4-dihydrophthalazine-1-carboxylic acidHCID 4311764Sodium borohydride2×

Product 1

HCID 126498924-(Hydroxymethyl)phthalazin-1(2H)-one

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

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.

Workup

  1. filtrationthe mixture is filtered
  2. washthe residue washed with 0.5 l THF
  3. temperatureThe yellow filtrate is cooled to 15° C.
  4. stirringthe suspension stirred for about 8 h at RT
  5. temperaturethe mixture heated for 5 h to 40° C
  6. stirringthe turbid solution is stirred for 30 min
  7. customthe aqueous phase is separated off
  8. extractionextracted 3 times with 2 l EtOAc
  9. washThe organic phases are washed twice each time with semisaturated brine and brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated by evaporation
  12. stirringStirring in water at 90° C.
  13. temperaturecooling
  14. filtrationfiltration

Sources & evidence

ORD record
ord-b9f31c0b0987460f974e3c24009475de
Source dataset
uspto-grants-2004_02
Patent number
US06686347B2

Reaction notes

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