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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 244461
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HRID 244461 반응식
[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
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참가 물질

5

반응물 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

생성물 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-one수율 26.3%

시약·촉매·용매 2

HCID 180Acetone용매2회
HCID 962Water용매2회

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-35884ba97a244bf5a5ea5c8585ee11df
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08658637B2

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