Water → Cp-195543

HRID 1278946노트

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HRID 1278946 반응식
CC(C)(C)C[O:4][C:5](=[O:34])[C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][C:7]=1[C:16]1[CH:25]=[C:24]2[C:19]([C@H:20]([OH:33])[C@@H:21]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH2:22][O:23]2)=[CH:18][CH:17]=1.[OH-].[Na+].O>C(O)(C)C>[CH2:26]([C@@H:21]1[C@@H:20]([OH:33])[C:19]2[C:24](=[CH:25][C:16]([C:7]3[CH:8]=[C:9]([C:12]([F:15])([F:13])[F:14])[CH:10]=[CH:11][C:6]=3[C:5]([OH:34])=[O:4])=[CH:17][CH:18]=2)[O:23][CH2:22]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

참가 물질

5

반응물 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 10918078(3S,4R)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid 2,2-dimethylpropyl ester

생성물 1

HCID 9823886Cp-195543수율 50.3%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

A solution of (3S, 4R)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid 2,2-dimethyl-propyl ester (2.34 g, 4.69 mmol) in isopropyl alcohol (23 mL) was treated with 10% aqueous sodium hydroxide (2.3 mL, 6.4 mmol) and heated at reflux for 3 hours. The reaction mixture was cooled to ambient temperature, poured into water (34 mL), and extracted with hexanes (23 mL) and isopropyl ether (13 mL). The aqueous layer was separated and extracted with hexanes (23 mL) and isopropyl ether (13 mL), adjusted to pH 2 with 6N aqueous hydrochloric acid, and extracted with ethyl acetate (two times 40 mL). The combined ethyl acetate extracts were washed with brine (40 mL), dried over magnesium sulfate, filtered and concentrated to a white foam which was recrystallized from toluene/hexanes. The resulting solids were filtered and washed with hexanes, and the wet cake was stirred with hexanes (20 mL) for 1 hour. The mixture was filtered, and the resulting solids were dried under vacuum to provide 1.01 g (50% yield) of (3S, 4R)-2-(3-benzyl-4-hydroxy-chroman-7-yl)-4-trifluoromethyl-benzoic acid as a white solid: 1H NMR (400 MHz, CDCl3) 67 8.00 (d, J=8.1 Hz, 1H), 7.67 (d, J=8.1 Hz, 1 H), 7.64 (s, 1 H), 7.18-7.36 (m, 6H), 6.91 (dd, J=7.9, 1.7 Hz, 1 H), 6.86 (d, J=1.7 Hz, 1 H), 4.53 (d, J=4.2 Hz, 1 H), 4.24 (dd, J=11.2, 2.7 Hz, 1 H), 3.97 (dd, J=11.0, 4.0 HZ, 1 H), 2.76 (dd, J=13.9, 6.4 Hz, 1 H), 2.53 (dd, J=13.7, 9.3 Hz, 1 H), 2.24-2.26 (m, 1 H).

후처리

  1. temperatureheated
  2. temperatureat reflux for 3 hours
  3. extractionextracted with hexanes (23 mL) and isopropyl ether (13 mL)
  4. customThe aqueous layer was separated
  5. extractionextracted with hexanes (23 mL) and isopropyl ether (13 mL)
  6. extractionextracted with ethyl acetate (two times 40 mL)
  7. washThe combined ethyl acetate extracts were washed with brine (40 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to a white foam which
  11. customwas recrystallized from toluene/hexanes
  12. filtrationThe resulting solids were filtered
  13. washwashed with hexanes
  14. filtrationThe mixture was filtered
  15. customthe resulting solids were dried under vacuum

출처 및 근거

ORD 기록
ord-6a641687541548149a454bd7be40d753
출처 데이터셋
uspto-grants-2002_09
특허 번호
US06444826B1

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