Hydrochloric Acid → HCID 86586746, compound

HRID 2088198Notes

Reaction equation

HRID 2088198 reaction equation
C([N:8]1[C@@H:13]2[C@H:14]([N:16]3[CH:20]=[N:19][N:18]=[CH:17]3)[CH2:15][C@@:9]1([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C@H:10]([O:21][C@H:22]([C:24]1[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]=1)[CH3:23])[CH2:11][CH2:12]2)C1C=CC=CC=1.[ClH:44]>CO.C(OCC)C.[OH-].[Pd+2].[OH-]>[ClH:44].[F:33][C:30]([F:31])([F:32])[C:28]1[CH:29]=[C:24]([C@@H:22]([O:21][C@@H:10]2[CH2:11][CH2:12][C@@H:13]3[NH:8][C@@:9]2([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:15][C@H:14]3[N:16]2[CH:17]=[N:18][N:19]=[CH:20]2)[CH3:23])[CH:25]=[C:26]([C:34]([F:35])([F:36])[F:37])[CH:27]=1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid2×HCID 86586748HCID 86586748, compound

Product 1

HCID 86586746HCID 86586746, compound

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent2×

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1S*)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-1-phenyl-6-(1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane (Example 133; 185 mg, 0.31 mmol) was dissolved in methanol (5 ml) and 2N hydrochloric acid (0.5 ml) and 10% palladium hydroxide (50 mg) added. The mixture was hydrogenated at 45 psi for 1.5 hours. The reaction mixture was filtered then concentrated in vacuo. The residue was partitioned between saturated sodium hydrogen carbonate solution and dichloromethane and the organics removed, dried (MgSO4) and concentrated in vacuo. The oil was purified by flash column chromatography [5% methanol in dichloromethane] and the hydrochloride salt was made by adding 1 equivalent of hydrogen chloride in diethyl ether (1.0M) to a solution in diethyl ether and the title compound filtered and dried in vacuo at 60° C. (27 mg, 16%).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthen concentrated in vacuo
  3. customThe residue was partitioned between saturated sodium hydrogen carbonate solution and dichloromethane
  4. dry with materialthe organics removed, dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe oil was purified by flash column chromatography [5% methanol in dichloromethane]
  7. filtrationthe title compound filtered
  8. customdried in vacuo at 60° C. (27 mg, 16%)

Sources & evidence

ORD record
ord-3b4fe5cf527a44e592803d519606e3e9
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

Loading…