Potassium Permanganate → 3-Hydroxymethyl-7-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-3,4-dihydropyrrolo[2,1-c][1,4]oxazin-1-one

HRID 244461Notes

Reaction equation

HRID 244461 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:33]C=C)[CH:8]=[C:9]([C:11]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[N:21]=[CH:20]3)([OH:16])[C:12]([F:15])([F:14])[F:13])[CH:10]=1)=[O:5])[CH3:2].[O-:36][Mn](=O)(=O)=O.[K+]>CC(C)=O.O>[OH:36][CH2:2][CH:1]1[O:3][C:4](=[O:5])[C:6]2=[CH:10][C:9]([C:11]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[N:22]([C:26]3[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=3)[N:21]=[CH:20]4)([OH:16])[C:12]([F:15])([F:13])[F:14])=[CH:8][N:7]2[CH2:33]1

Participants

5

Reactant 2

HCID 516875Potassium PermanganateHCID 249590981-allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid ethyl ester

Product 1

HCID 594373173-Hydroxymethyl-7-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-3,4-dihydropyrrolo[2,1-c][1,4]oxazin-1-oneYield 26.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent2×

Procedure

To a chilled (0° C.) solution of 1-allyl-4-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}-1H-pyrrole-2-carboxylic acid ethyl ester (100 mg, 0.2 mmol, 1 equiv.) in 3 mL of acetone and 1 mL of water was added a solution of KMnO4 (39 mg, 0.25 mmol, 1.2 equiv.) in 3 mL of acetone and 1 mL of water. The ice bath was removed and the reaction was warmed to room temperature. After 2 hours, the reaction was filtered through CELITE® filter aid and the filter cake washed with acetone. The filtrate was concentrated in vacuo diluted with water and extracted with EtOAc. The combined organic layers were dried, filtered, and concentrated in vacuo. The residue was purified by reverse phase HPLC (5-95% CH3CN/water 0.1% TFA). The fractions were combined and concentrated to remove CH3CN. The aqueous residue was made basic with saturated aqueous sodium bicarbonate and extracted with EtOAc to provide 25 mg of the title compound as a white solid. MS m/z 476.16 (MH+).

Workup

  1. customThe ice bath was removed
  2. filtrationthe reaction was filtered through CELITE®
  3. filtrationfilter aid
  4. washthe filter cake washed with acetone
  5. concentrationThe filtrate was concentrated in vacuo
  6. additiondiluted with water
  7. extractionextracted with EtOAc
  8. customThe combined organic layers were dried
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by reverse phase HPLC (5-95% CH3CN/water 0.1% TFA)
  12. concentrationconcentrated
  13. customto remove CH3CN
  14. extractionextracted with EtOAc

Sources & evidence

ORD record
ord-35884ba97a244bf5a5ea5c8585ee11df
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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