Hydrogen Peroxide → 2-(4-Benzyloxy-3,5-difluoro-phenyl)-cyclopropanecarboxylic acid

HRID 62904Notes

Reaction equation

HRID 62904 reaction equation
[Li+].[OH-:2].OO.C([C@@H]1COC(=O)N1C([CH:20]1[CH2:22][CH:21]1[C:23]1[CH:28]=[C:27]([F:29])[C:26]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:25]([F:38])[CH:24]=1)=O)C1C=CC=CC=1.[O-]S([O-])=O.[Na+].[Na+].C1[CH2:49][O:48]CC1.O>O>[CH2:31]([O:30][C:26]1[C:27]([F:29])=[CH:28][C:23]([CH:21]2[CH2:22][CH:20]2[C:49]([OH:48])=[O:2])=[CH:24][C:25]=1[F:38])[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

7

Reactant 5

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 24437Sodium SulfiteHCID 21881883Oxolane--water (1/1)HCID 90118118(R)-4-benzyl-3-[2-(4-benzyloxy-3,5-difluoro-phenyl)-cyclopropanecarbonyl]-oxazolidin-2-on

Product 1

HCID 901182402-(4-Benzyloxy-3,5-difluoro-phenyl)-cyclopropanecarboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

After LiOH (6.4 mg, 0.152 mmol) was dissolved in water (1 mL), H2O2 (35%, 37 mg, 0.38 mmol) was added thereto, and the mixture was stirred at room temperature for 30 minutes, and then cooled to 0° C. The reactant was added to the solution of (R)-4-benzyl-3-[2-(4-benzyloxy-3,5-difluoro-phenyl)-cyclopropanecarbonyl]-oxazolidin-2-on (less polar, 44 mg, 0.095 mmol) obtained in Step B of Preparation Example 58 dissolved in THF/H2O (2 mL/0.5 mL), and the mixture was stirred for 1 hour. After the termination of the reaction, Na2SO3 solution (0.1 g in 1 mL of H2O) was added thereto, and the mixture was stirred at 0° C. for 1 hour, and then concentrated under reduced pressure. The residue was added with water, and 6N HCl aqueous solution was added to adjust the pH of the solution to 2. The organic layer obtained by the extraction with ethyl acetate was separated, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain the mixture (41 mg) of the title compound and 4-benzyloxazolidin-2-on, which was used in the next step without a separate purification process.

Workup

  1. temperaturecooled to 0° C
  2. customobtained in Step B of Preparation Example 58
  3. stirringthe mixture was stirred for 1 hour
  4. additionwas added
  5. stirringthe mixture was stirred at 0° C. for 1 hour
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was added with water, and 6N HCl aqueous solution
  8. additionwas added
  9. customThe organic layer obtained by the extraction with ethyl acetate
  10. customwas separated
  11. dry with materialdried with anhydrous magnesium sulfate
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-57d96369d3eb427788d6186785596aa0
Source dataset
uspto-grants-2016_09
Patent number
US09447044B2

Reaction notes

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