p-Toluenesulfonic acid → HCID 86628116, compound

HRID 2245251Notes

Reaction equation

HRID 2245251 reaction equation
[NH2:1][CH2:2][C@@H:3]1[C@@H:8]([C:9](OCC)=[O:10])[C@H:7]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@@H:6]([O:21][C@@H:22]([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)[CH3:23])[CH2:5][CH2:4]1.[C:38]1(=O)[CH2:42][CH2:41][C:40](=[O:43])[CH2:39]1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:31][C:30]([F:32])([F:33])[C:28]1[CH:29]=[C:24]([C@H:22]([O:21][C@H:6]2[CH2:5][CH2:4][C@H:3]([CH2:2][NH:1][C:38]3[CH2:42][CH2:41][C:40](=[O:43])[CH:39]=3)[C@@H:8]([CH2:9][OH:10])[C@@H:7]2[C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH3:23])[CH:25]=[C:26]([C:34]([F:36])([F:37])[F:35])[CH:27]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 774661,3-CyclopentanedioneHCID 86628115Ethyl (1R,2R,3S,6S)-6-(aminomethyl)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)cyclohexanecarboxylate2×

Product 1

HCID 86628116HCID 86628116, compoundYield 10.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl (1R,2R,3S,6S)-6-(aminomethyl)-3-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-2-(4-fluorophenyl)cyclohexanecarboxylate (0.07 g, 0.13 mmol, intermediate from Step E) in 30 mL dry toluene was added cyclopentane-1,3-dione (0.064 g, 0.65 mmol) and a catalytic amount (˜0.5 mg) of PTSA. The resulting mixture was heated at reflux for 1 hr. The solvent was removed under vacuum. The residue was dissolved in 10 mL toluene and was cooled to −78° C. under nitrogen. Dibal-H (2 mL, 1.0 M) was added. The reaction mixture was stirred for 16 hr at −78° C., quenched with water and diluted with ethyl acetate (10 mL). The organic layer was separated and the aqueous was extracted with ethyl acetate (10 mL). The combined extracts were washed with brine, dried over MgSO4, filtered and the solvent was removed under vacuum. The residue was purified by preparative TLC (silica gel eluting with 9:1 ethyl acetate: methanol) to give 8 mg of the title compound. MS: (MH)+ 574.2. The rest of the material was still unreacted ester.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 1 hr
  3. customThe solvent was removed under vacuum
  4. dissolutionThe residue was dissolved in 10 mL toluene
  5. additionDibal-H (2 mL, 1.0 M) was added
  6. customquenched with water
  7. additiondiluted with ethyl acetate (10 mL)
  8. customThe organic layer was separated
  9. extractionthe aqueous was extracted with ethyl acetate (10 mL)
  10. washThe combined extracts were washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customthe solvent was removed under vacuum
  14. customThe residue was purified by preparative TLC (silica gel eluting with 9:1 ethyl acetate: methanol)

Sources & evidence

ORD record
ord-54fb843ef75b45fab0065de46c56dac2
Source dataset
uspto-grants-2010_03
Patent number
US07683068B2

Reaction notes

Loading…