Trifluoroacetic acid → N-((1R,2S)-2-{[(4aR*,5R*,10bR*)-5-Phenyl-3,4,4a,5,6,10b-hexahydrobenzo[h]-1,6-naphthyridin-1(2H)-yl]carbonyl}cyclohexyl)benzamide

HRID 735779Notes

Reaction equation

HRID 735779 reaction equation
C(O)(C(F)(F)F)=O.[C:8]1([C@@H:14]2[NH:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[C@H:20]3[C@@H:15]2[CH2:16][CH2:17][CH2:18][N:19]3[C:28]([C@H:30]2[CH2:35][CH2:34][CH2:33][CH2:32][C@H:31]2[NH:36][C:37](=[O:43])OC(C)(C)C)=[O:29])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[OH-].[Na+].C(Cl)(=O)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>O>[C:8]1([C@@H:14]2[NH:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[C@H:20]3[C@@H:15]2[CH2:16][CH2:17][CH2:18][N:19]3[C:28]([C@H:30]2[CH2:35][CH2:34][CH2:33][CH2:32][C@H:31]2[NH:36][C:37](=[O:43])[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:29])[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7412Benzoyl chlorideHCID 14798Sodium HydroxideHCID 57847269tert-Butyl ((1R,2S)-2-{[(4aR*,5R*,10bR*)-5-phenyl-3,4,4a,5,6,10b-hexahydrobenzo[h]-1,6-naphthyridin-1(2H)-yl]carbonyl}cyclohexyl)carbamate

Product 1

HCID 57847030N-((1R,2S)-2-{[(4aR*,5R*,10bR*)-5-Phenyl-3,4,4a,5,6,10b-hexahydrobenzo[h]-1,6-naphthyridin-1(2H)-yl]carbonyl}cyclohexyl)benzamideYield 65.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

TFA (1 ml) was added to tert-butyl ((1R,2S)-2-{[(4aR*,5R*,10bR*)-5-phenyl-3,4,4a, 5,6,10b-hexahydrobenzo[h]-1,6-naphthyridin-1(2H)-yl]carbonyl}cyclohexyl)carbamate (69 mg, 0.14 mmol), and the mixture was stirred at room temperature for 3 min. Ice was added to the reaction solution, and the mixture was basified with 8N aqueous sodium hydroxide solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried (over anhydrous MgSO4), and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in dimethylacetamide (2 ml), benzoyl chloride (28 mg, 0.17 mmol) was added at 0° C., and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with 6% aqueous sodium hydrogen carbonate solution and saturated brine, dried (over anhydrous MgSO4), and the solvent was evaporated under reduced pressure. The residue was subjected to column chromatography using silica gel (10 g), and eluted with hexane-ethyl acetate (7:1-3:1, v/v) to give the title compound (45 mg, 65%) as a colorless amorphous form.

Workup

  1. additionIce was added to the reaction solution
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried (over anhydrous MgSO4)
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe obtained residue was dissolved in dimethylacetamide (2 ml)
  7. stirringthe mixture was stirred at room temperature for 1 hr
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with 6% aqueous sodium hydrogen carbonate solution and saturated brine
  10. dry with materialdried (over anhydrous MgSO4)
  11. customthe solvent was evaporated under reduced pressure
  12. washeluted with hexane-ethyl acetate (7:1-3:1

Sources & evidence

ORD record
ord-7dfe26100f204f2aa9ee651ec0d5d3fd
Source dataset
uspto-grants-2009_09
Patent number
US07592453B2

Reaction notes

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