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

HRID 2423501노트

반응식

HRID 2423501 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
90 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-975b1a2a472342cc991273d43fcbad2e
출처 데이터셋
uspto-grants-2011_06
특허 번호
US07960552B2

반응 노트

불러오는 중…