Hydrogen Peroxide → HCID 19697340, compound

HRID 862377Notes

Reaction equation

HRID 862377 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[C:17](=[O:18])[C:16]3[CH2:15][CH:14]=[CH:13][CH2:12][C:11]=3[C:10]2=[O:19])=[C:4]([F:20])[CH:3]=1.[OH-:21].[Na+].O.OO>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N:9]2[C:10](=[O:19])[C:11]3[CH2:12][CH:13]([OH:21])[CH2:14][CH2:15][C:16]=3[C:17]2=[O:18])=[C:4]([F:20])[CH:3]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 962WaterHCID 14798Sodium HydroxideHCID 19697344HCID 19697344, compound

Product 1

HCID 19697340HCID 19697340, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 500 mg(1.61 mmol) of 2-(4-chloro-2-fluoro-5-hydroxyphenyl)-4,7-dihydro-1H-isoindole-1,3(2H)-dione in 10 mL of tetrahydrofuran (THF) was added 1.94 mL of a 1M solution of BH3 in THF at 0° C. The mixture was then stirred at the same temperature for 1 h. Then, the mixture was warmed to room temperature. A solution of 3.0 mL of 6N aqueous sodium hydroxide, 1.8 mL of water, and 2.1 mL of 30% aqueous hydrogen peroxide were added subsequently. The mixture was stirred at the same temperature for 4 h. The crude product was diluted with ethyl acetate. The organic layer was washed with water, dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography over silica gel, eluting with a 1:2 v:v mixture of ethyl acetate and n-hexane to give 62 mg of the title product of Step B, a compound of the invention, as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 1.8 (br s, 1H), 1.95 (m, 2H), 2.8-2.4 (m, 4H), 4.4 (m, 1H), 5.85 (br s, 1H), 6.9 (s, 1H), 7.5 (s, 1H).

Workup

  1. stirringThe mixture was stirred at the same temperature for 4 h
  2. washThe organic layer was washed with water
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by flash chromatography over silica gel
  6. washeluting with a 1:2 v
  7. additionv mixture of ethyl acetate and n-hexane

Sources & evidence

ORD record
ord-5bfff28166714b6298c3dfb53131cc32
Source dataset
uspto-grants-1998_02
Patent number
US05719104

Reaction notes

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