Hydrochloric Acid → (1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-{2-(1,2,4-triazol-1-yl)ethyl}-8-azabicyclo[3.2.1]octane hydrochloride

HRID 2088164Notes

Reaction equation

HRID 2088164 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.[OH-].[Na+].[F:8][C:9]([F:44])([F:43])[C:10]1[CH:11]=[C:12]([CH2:20][O:21][C@@H:22]2[CH2:28][CH2:27][C@@H:26]3[N:29]([CH2:30][CH2:31]OS(C)(=O)=O)[C@@:23]2([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:24][CH2:25]3)[CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:15]=1.[ClH:45]>C(#N)C.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O.C(OCC)C>[ClH:45].[F:18][C:16]([F:17])([F:19])[C:14]1[CH:13]=[C:12]([CH2:20][O:21][C@@H:22]2[CH2:28][CH2:27][C@@H:26]3[N:29]([CH2:30][CH2:31][N:1]4[CH:5]=[N:4][CH:3]=[N:2]4)[C@@:23]2([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:24][CH2:25]3)[CH:11]=[C:10]([C:9]([F:44])([F:8])[F:43])[CH:15]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 92571H-1,2,4-TriazoleHCID 14798Sodium HydroxideHCID 86586697(1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-8-(2-mesyloxyethyl)-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586698(1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-{2-(1,2,4-triazol-1-yl)ethyl}-8-azabicyclo[3.2.1]octane hydrochloride

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

1,2,4-Triazole (25 mg, 0.37 mmol) was dissolved in acetonitrile (2 ml) and sodium hydroxide (44 mg, 1.11 mmol). This was stirred at room temperature for 30 minutes then tetrabutylammonium hydrogen sulphate and (1R*,2R*,5R*)-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-8-(2-mesyloxyethyl)-1-phenyl-8-azabicyclo[3.2.1]octane (Example 68; 201 mg, 0.37 mmol) added. The reaction was heated to reflux for 2.5 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (×3), dried (MgSO4), and concentrated in vacuo to give a brown oil. This was purified by flash column chromatography [5% methanol in dichloromethane] to give a brown oil and the hydrochloride salt was made by adding 1 equivalent of hydrogen chloride in diethyl ether (1N) and the title compound filtered off and dried in vacuo at 60° C.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2.5 hours
  3. extractionextracted with ethyl acetate (×3)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customto give a brown oil
  7. customThis was purified by flash column chromatography [5% methanol in dichloromethane]
  8. customto give a brown oil
  9. filtrationthe title compound filtered off
  10. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-c0bab8212bab43a4935879761f07d7ab
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

Loading…