Sodium methanolate methanol → 4-(4-Fluoro-benzyl)-1-hydroxy-3-oxo-6-trifluoromethyl-3,4-dihydro-4,4a-diaza-fluorene-2-carboxylic acid methyl ester

HRID 1512007ノート

反応式

HRID 1512007 の反応式
C([O:3][C:4]([C:6]1[N:7]([N:19]([C:28](=[O:35])[CH2:29][C:30]([O:32][CH2:33]C)=[O:31])[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([C:15]([F:18])([F:17])[F:16])[CH:9]=2)=O)C.C[O-].[Na+].CO>>[CH3:33][O:32][C:30]([C:29]1[C:28](=[O:35])[N:19]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[N:7]2[C:6](=[CH:14][C:13]3[C:8]2=[CH:9][C:10]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:12]=3)[C:4]=1[OH:3])=[O:31]

参加物

3

反応物 2

HCID 23694274Sodium methanolate methanolHCID 672304801-[(2-Ethoxycarbonyl-acetyl)-(4-fluoro-benzyl)-amino]-6-trifluoromethyl-1H-indole-2-carboxylic acid ethyl ester

生成物 1

HCID 687624054-(4-Fluoro-benzyl)-1-hydroxy-3-oxo-6-trifluoromethyl-3,4-dihydro-4,4a-diaza-fluorene-2-carboxylic acid methyl ester収率 22.3%

実験手順

A mixture of 1-[(2-ethoxycarbonyl-acetyl)-(4-fluoro-benzyl)-amino]-6-trifluoromethyl-1H-indole-2-carboxylic acid ethyl ester (160 mg, 0.32 mmol) in 0.5 N NaOMe/MeOH solution (2.5 mL, 1.25 mmol) was refluxed overnight. After cooled, the mixture was concentrated, and the residue was dissolved in water (80 mL), acidified to pH=3-4 using 1 N HCl solution, extracted with EtOAc (2 times). Combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. Crude product was purified by silica gel chromatography (50%-100% EtOAc/DCM then 2%-10% MeOH/DCM) to provide the title compound 31 mg. ESI (m/z): 435.14 (M+H)+.

後処理

  1. temperaturewas refluxed overnight
  2. temperatureAfter cooled
  3. concentrationthe mixture was concentrated
  4. dissolutionthe residue was dissolved in water (80 mL)
  5. extractionextracted with EtOAc (2 times)
  6. washCombined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customCrude product was purified by silica gel chromatography (50%-100% EtOAc/DCM

出典と根拠

ORDレコード
ord-03b56b5388634c7a80d6d801f4e57349
出典データセット
uspto-grants-2012_07
特許番号
US08217043B2

反応ノート

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