Hydrochloric Acid → 6-[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-7-fluoro-2-quinolinecarboxylic acid

HRID 2423501ノート

反応式

HRID 2423501 の反応式
[OH-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:5]=1[C:11]1[C:15]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][C:33]=3[F:34])[N:30]=[C:29]([C:35]([O:37]CC)=[O:36])[CH:28]=[CH:27]4)=[CH:20][CH:19]=2)=[C:14]([CH:40]([CH3:42])[CH3:41])[O:13][N:12]=1.Cl.O>O1CCCC1.CO>[Cl:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([Cl:3])[C:5]=1[C:11]1[C:15]([CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][C:33]=3[F:34])[N:30]=[C:29]([C:35]([OH:37])=[O:36])[CH:28]=[CH:27]4)=[CH:22][CH:23]=2)=[C:14]([CH:40]([CH3:42])[CH3:41])[O:13][N:12]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 59321487Ethyl 6-[4-({[3-(2,6-dichlorophenyl)-5(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-7-fluoro-2-quinolinecarboxylate

生成物 1

HCID 533187586-[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-7-fluoro-2-quinolinecarboxylic acid収率 95.3%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
90 °C

実験手順

A 1 N solution of sodium hydroxide (154.6 μL, 154.6 μmol) was added to ethyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-7-fluoro-2-quinolinecarboxylate (44.8 mg, 77.3 μmol) in tetrahydrofuran and methanol (1:1, 1.6 mL) and the mixture was heated in the microwave at 90° C. for 10 minutes. After cooling, the mixture was neutralized with 1 N hydrochloric acid (154.6 μL), water added, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, then dried over anhydrous magnesium sulfate, filtered and concentrated to give 40.6 mg (95%) of 6-[4-({[3-(2,6-Dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-7-fluoro-2-quinolinecarboxylic acid as a solid. 1H NMR (400 MHz, d6-DMSO): δ 13.52 (br s, 1H), 8.56 (d, J=9 Hz, 1H), 8.21 (d, J=9 Hz, 1H), 8.09 (d, J=9 Hz, 1H), 7.98 (d, J=12 Hz, 1H), 7.65-7.61 (m, 2H), 7.56 (d, J=9 Hz, 2H), 7.56-7.52 (m, 1H), 6.96 (d, J=9 Hz, 2H), 4.90 (s, 2H), 3.48 (septet, J=7 Hz, 1H), 1.34 (d, J=7 Hz, 6H). HRMS C29H21Cl2FN2O4 m/z 551.0941 (M+H)+Cal; 551.0952 (M+H)+Obs.

後処理

  1. temperatureAfter cooling
  2. additionadded
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-975b1a2a472342cc991273d43fcbad2e
出典データセット
uspto-grants-2011_06
特許番号
US07960552B2

反応ノート

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