Triethylamine → 4-[4-(Hydroxyaminocarbonyl)methoxy-3,5-dimethyphenyl]-2-methyl-1(2H)phthalazinone

HRID 1953812Notes

Reaction equation

HRID 1953812 reaction equation
[C:1]([CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:23])[N:15]([CH3:24])[N:14]=2)=[CH:8][C:7]=1[CH3:25])(O)=[O:2].C(N(CC)CC)C.ClC(OC(C)=C)=O.[Si]([O:47][NH2:48])(C(C)(C)C)(C)C>ClCCl>[OH:47][NH:48][C:1]([CH2:4][O:5][C:6]1[C:7]([CH3:25])=[CH:8][C:9]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16](=[O:23])[N:15]([CH3:24])[N:14]=2)=[CH:10][C:11]=1[CH3:12])=[O:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 93846Isopropenyl chloroformateHCID 4691350O-(tert-Butyldimethylsilyl)hydroxylamineHCID 700083854-[4-(Carboxy)methoxy-3,5-dimethyphenyl]-2-methyl-1(2H)phthalazinone

Product 1

HCID 179185964-[4-(Hydroxyaminocarbonyl)methoxy-3,5-dimethyphenyl]-2-methyl-1(2H)phthalazinoneYield 8.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of example 108 (1.15 g) in dichloromethane (30 ml) at 0° C. was treated with triethylamine (0.52 g) followed by isopropenyl chloroformate (0.41 g), and the mixture was stirred for 1 h. O-tert-butyldimethylsilylhydroxylamine (0.50 g) was then added and the mixture was stirred for a further 18 h. The reaction mixture was washed with 10% citric acid (20 ml), saturated sodium bicarbonate (20 ml) and the concentrated to dryness in vacuo. A solution of the residual solid in tetrahydrofuran (30 ml) and water (5 ml) was then treated with a 1.0 M solution of tetrabutylammonium fluoride in tetahydrofuran (1 ml) and stirred 1 h the resultant crude mixture was concentrated on to silica and purified by chromatography, eluting with 5% methanol in dichloromethane, to provide the title compound as a white solid (0.10 g).

Workup

  1. stirringthe mixture was stirred for a further 18 h
  2. washThe reaction mixture was washed with 10% citric acid (20 ml), saturated sodium bicarbonate (20 ml)
  3. concentrationthe concentrated to dryness in vacuo
  4. additionA solution of the residual solid in tetrahydrofuran (30 ml) and water (5 ml) was then treated with a 1.0 M solution of tetrabutylammonium fluoride in tetahydrofuran (1 ml)
  5. stirringstirred 1 h the resultant crude mixture
  6. concentrationwas concentrated on to silica
  7. custompurified by chromatography
  8. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-a7fad0d52b764d34b4897ee33808c147
Source dataset
uspto-grants-2000_09
Patent number
US06118001

Reaction notes

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