Diethyl Pyrocarbonate → 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

HRID 550287Notes

Reaction equation

HRID 550287 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]3C(OC(C)(C)C)=O)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[OH-].[Na+].[C:37]([O:41][C:42]([NH:44][C@@H:45]1[CH2:50][CH2:49][CH2:48][CH2:47][C@@H:46]1[C:51](O)=[O:52])=[O:43])([CH3:40])([CH3:39])[CH3:38].C(N(CC)CC)C.CCOC(OC(OCC)=O)=O>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:51]([C@H:46]2[CH2:47][CH2:48][CH2:49][CH2:50][C@H:45]2[NH:44][C:42](=[O:43])[O:41][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:52])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 6

HCID 3051Diethyl PyrocarbonateHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 1512489(1S,2R)-2-(((tert-butoxy)carbonyl)amino)cyclohexane-1-carboxylic acidHCID 67150493tert-butyl (4aR*,5R*,10bR*)-5-phenyl-3,4,4a,5,6,10b-hexahydrobenzo[h]-1,6-naphthyridine-1(2H)-carboxylate

Product 1

HCID 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)carbamateYield 26.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

TFA (1 ml) was added to tert-butyl (4aR*,5R*,10bR*)-5-phenyl-3,4,4a,5,6,10b-hexahydrobenzo[h]-1,6-naphthyridine-1(2H)-carboxylate (195 mg, 0.54 mmol), and the mixture was stirred at room temperature for 3 min. Ice water was added to the reaction mixture, basified with 8N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried (over anhydrous MgSO4), and the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (3 ml), (1S,2R)-2-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid (131 mg, 0.54 mmol) and triethylamine (109 mg, 1.1 mmol) were added, DEPC (88 mg, 0.54 mmol) was added at 0° C., and the mixture was stirred overnight at room temperature. 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 (30 g), and eluted with hexane-ethyl acetate (9:1-4:1, v/v) to give the title compound (69 mg, 26%) as a colorless amorphous form.

Workup

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

Sources & evidence

ORD record
ord-6442b8e37e1e425e99cc277efe4ff49e
Source dataset
uspto-grants-2011_05
Patent number
US07943770B2

Reaction notes

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