Trifluoroacetic acid → HCID 69033916, compound

HRID 351367Notes

Reaction equation

HRID 351367 reaction equation
C(O[C:6](=[O:35])[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C@H:13]2[CH2:18][CH2:17][C@@H:16]([N:19]=[N+]=[N-])[CH2:15][C@H:14]2[CH2:22][S:23]([C:26]2[CH:31]=[CH:30][C:29](SC)=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:9]1=[O:34])(C)(C)C.[C:36](O)([C:38]([F:41])([F:40])[F:39])=O>C(Cl)Cl>[C:26]1([S:23]([CH2:22][C@@H:14]2[CH2:15][C@H:16]([NH:19][CH:8]([CH3:12])[CH3:9])[CH2:17][CH2:18][C@@H:13]2[N:10]2[CH2:11][CH2:12][C@H:8]([NH:7][C:6](=[O:35])[C:14]3[CH:13]=[CH:18][CH:17]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:15]=3)[C:9]2=[O:34])(=[O:24])=[O:25])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86594360HCID 86594360, compound

Product 1

HCID 69033916HCID 69033916, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

{(3S)-1-[(1S,2R,4R)-4-Azido-2-(4-methylsulfanyl-benzenesulfonylmethyl)-cyclohexyl]-2-oxo-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (240 mg), see example 18, was dissolved in CH2Cl2 (5 mL) prior to the addition of TFA (2.5 mL). After 30 min, it was concentrated and dried. The resulting residue was dissolved in DMF prior to the addition of 4-methylmorpholine (0.25 mL) and 3-trifluoromethyl-benzoic acid (104.5 mg). BOP Reagent (64 mg) was added and the mixture was stirred for 40 min. After concentration, EtOAc was added along with 1N HCl solution. The EtOAc layer was washed with NaHCO3 solution (aq) and brine, dried (MgSO4), filtered, and concentrated. This material was passed through a plug of silica and concentrated. The resulting material (178 mg) was dissolved in MeOH (5 mL) prior to the addition of 20% Pd(OH)2 (100 mg). A hydrogen balloon was added and the mixture was stirred. After stirring overnight, the palladium was filtered off and the solvent was concentrated. A portion of this material (68 mg) was dissolved in dichloroethane (2.5 mL) prior to the adddition of acetone (0.04 mL) and NaBH(OAc)3 (64 mg). After 40 min, the solution was concentrated. The resulting residue was dissolved in EtOAc and washed with saturated NaHCO3. The organic layer was dried, filtered, and concentrated. Reverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) of the resulting residue provided the title compound (66 mg). MS found: (M+H)+=566.4.

Workup

  1. concentrationit was concentrated
  2. customdried
  3. dissolutionThe resulting residue was dissolved in DMF
  4. additionto the addition of 4-methylmorpholine (0.25 mL) and 3-trifluoromethyl-benzoic acid (104.5 mg)
  5. additionBOP Reagent (64 mg) was added
  6. concentrationAfter concentration, EtOAc
  7. additionwas added along with 1N HCl solution
  8. washThe EtOAc layer was washed with NaHCO3 solution (aq) and brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. concentrationconcentrated
  13. dissolutionThe resulting material (178 mg) was dissolved in MeOH (5 mL)
  14. additionto the addition of 20% Pd(OH)2 (100 mg)
  15. additionA hydrogen balloon was added
  16. stirringthe mixture was stirred
  17. stirringAfter stirring overnight
  18. filtrationthe palladium was filtered off
  19. concentrationthe solvent was concentrated
  20. dissolutionA portion of this material (68 mg) was dissolved in dichloroethane (2.5 mL)
  21. waitAfter 40 min
  22. concentrationthe solution was concentrated
  23. dissolutionThe resulting residue was dissolved in EtOAc
  24. washwashed with saturated NaHCO3
  25. customThe organic layer was dried
  26. filtrationfiltered
  27. concentrationconcentrated
  28. customReverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) of the resulting residue

Sources & evidence

ORD record
ord-a021b13501e74f37bee7f585f2ad0f8c
Source dataset
uspto-grants-2007_02
Patent number
US07183270B2

Reaction notes

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