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ノート

反応式

HRID 244461 の反応式
[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

参加物

5

反応物 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

生成物 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-one収率 26.3%

試薬・触媒・溶媒 2

HCID 180Acetone溶媒2 回HCID 962Water溶媒2 回

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-35884ba97a244bf5a5ea5c8585ee11df
出典データセット
uspto-grants-2014_02
特許番号
US08658637B2

反応ノート

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