Water → Cp-195543

HRID 277456Notes

Reaction equation

HRID 277456 reaction equation
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

Participants

5

Reactant 3

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

Product 1

HCID 9823886Cp-195543Yield 50.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

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) δ8.00 (d, J=8.1 Hz, 1H), 7.67 (d, J=8.1 Hz, 1H), 7.64 (s, 1H), 7.18-7.36 (m, 6H), 6.91 (dd, J=7.9, 1H), 6.86 (d, J=1.7 Hz, 1H), 4.53 (d, J=4.2 Hz, 1H), 4.24 (dd, J=11.2, 2.7 Hz, 1H), 3.97 (dd, J=11.0, 4.0 HZ, 1H), 2.76 (dd, J=13.9, 6.4 Hz, 1H), 2.53 (dd, J=13.7, 9.3 Hz, 1H), 2.24-2.26 (m, 1H).

Workup

  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

Sources & evidence

ORD record
ord-338c72f5d4a848c8859016123230099d
Source dataset
uspto-grants-2002_03
Patent number
US06355825B1

Reaction notes

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