Water → HCID 22279973, compound

HRID 1063421Notes

Reaction equation

HRID 1063421 reaction equation
[CH2:1]([N:8]([CH2:16][CH:17]1[CH2:21][O:20][CH:19]([O:22][C:23](=O)[C:24]2[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=2)[CH:18]1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[C:46](OCC)(=O)C>O1CCCC1>[CH2:9]([N:8]([CH2:16][CH:17]1[CH:18]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:19]([O:22][C:23]([C:24]2[CH:25]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=2)=[CH2:46])[O:20][CH2:21]1)[CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 962WaterHCID 8857Ethyl AcetateHCID 23401464HCID 23401464, compound

Product 1

HCID 22279973HCID 22279973, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

(2SR, 3SR, 4SR) 3,5-Bis(trifluoromethyl)benzoic acid 4-[(N,N-dibenzylamino)methyl]-3-phenyl-tetrahydrofuran-2-yl ester (Description 7(a); 1.03 g, 1.7 mmol) was azeotroped with tetrahydrofuran (2×10 ml), dissolved in tetrahydrofuran (15 ml) and degassed with Firestone™ valve (×3). Bis(cyclopentadiene) titanium dimethyl (1.8 ml, 2.8M in toluene) was added and the mixture was heated to 60° C. in the dark. Further bis(cyclopentadiene) titanium dimethyl (1 ml) was added and the reaction was left to stand for 18 hours. The reaction was quenched with a slurry of sodium carbonate (4 g), water (2.5 ml) and methanol (50 ml), which caused it to turn yellow, and the reaction was left to stand at 40° C. for 16 hours under nitrogen. The solid was removed by filtration and the solvent removed in vacuo to afford a yellow solid. The solid was dispersed between water (50 ml) and ethyl acetate (40 ml), the aqueous layer was washed with ethyl acetate (3×20 ml) and brine (1×50 ml), and dried over MgSO4. The solvent was removed in vacuo and the product purified by flash column chromatography on silica gel and eluting in increasing concentrations of dichloromethane in hexane (10-100%) to give the title compound (299 mg, yield 29%).

Workup

  1. customdegassed with Firestone™ valve (×3)
  2. additionBis(cyclopentadiene) titanium dimethyl (1.8 ml, 2.8M in toluene) was added
  3. additionFurther bis(cyclopentadiene) titanium dimethyl (1 ml) was added
  4. waitthe reaction was left
  5. customThe reaction was quenched with a slurry of sodium carbonate (4 g), water (2.5 ml) and methanol (50 ml), which
  6. waitthe reaction was left
  7. waitto stand at 40° C. for 16 hours under nitrogen
  8. customThe solid was removed by filtration
  9. customthe solvent removed in vacuo
  10. customto afford a yellow solid
  11. washthe aqueous layer was washed with ethyl acetate (3×20 ml) and brine (1×50 ml)
  12. dry with materialdried over MgSO4
  13. customThe solvent was removed in vacuo
  14. customthe product purified by flash column chromatography on silica gel
  15. washeluting
  16. temperaturein increasing concentrations of dichloromethane in hexane (10-100%)

Sources & evidence

ORD record
ord-81e500672a0c4a56a276efcbcef18247
Source dataset
uspto-grants-2005_11
Patent number
US06964981B2

Reaction notes

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