Hydrogen Peroxide → (4-fluoro-phenyl)-(3-hydroxy-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-methanone

HRID 1773803Notes

Reaction equation

HRID 1773803 reaction equation
[OH-:1].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:17][CH2:16][N:15]3[N:18]=[C:19]([CH2:24][O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:20](B(O)O)=[C:14]3[CH2:13]2)=[O:11])=[CH:6][CH:5]=1.OO>C1COCC1>[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:17][CH2:16][N:15]3[N:18]=[C:19]([CH2:24][O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:20]([OH:1])=[C:14]3[CH2:13]2)=[O:11])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 67960230{5-[(4-Fluorophenyl)carbonyl]-2-(phenoxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl}boronic acid

Product 1

HCID 67960185(4-fluoro-phenyl)-(3-hydroxy-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-methanoneYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 2M aqueous solution of sodium hydroxide (0.53 mL, 1.06 mmol) was added to a stirred solution of {5-[(4-fluorophenyl)carbonyl]-2-(phenoxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl}boronic acid (0.21 g, 0.53 mmol) and hydrogen peroxide (0.084 mL, 1.06 mmol) in THF (5.3 mL) at 0° C. The mixture was stirred at room temperature for 16 hours. Then the solvent was evaporated in vacuo and the crude product was purified by flash column chromatography (silica; 7N solution of ammonia in methanol in DCM 0/100 to 5/95). The desired fractions were collected and the solvents evaporated in vacuo to yield (4-fluoro-phenyl)-(3-hydroxy-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-methanone (19 mg, 10% yield) as a colourless oil.

Workup

  1. customThen the solvent was evaporated in vacuo
  2. customthe crude product was purified by flash column chromatography (silica; 7N solution of ammonia in methanol in DCM 0/100 to 5/95)
  3. customThe desired fractions were collected
  4. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-99bf76b45b9e4438996b9a96a834f108
Source dataset
uspto-grants-2016_02
Patent number
US09255103B2

Reaction notes

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