Hydrochloric Acid → HCID 86586728, compound

HRID 2088186Notes

Reaction equation

HRID 2088186 reaction equation
C([N:8]1[C@@H:13]2[C@H:14]([N:16]3[C:20]([CH3:21])=[N:19][N:18]=[N: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:22][CH2:23][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)[CH2:11][CH2:12]2)C1C=CC=CC=1.[ClH:44]>CO.C(OCC)C.[OH-].[Pd+2].[OH-]>[ClH:44].[F:32][C:30]([F:31])([F:33])[C:28]1[CH:29]=[C:24]([CH2:23][O:22][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[C:20]([CH3:21])=[N:19][N:18]=[N:17]2)[CH:25]=[C:26]([C:34]([F:35])([F:37])[F:36])[CH:27]=1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid2×HCID 86586727HCID 86586727, compound

Product 1

HCID 86586728HCID 86586728, compound

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolvent2×

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-(5-methyl-1H-tetrazol-1-yl)-1-phenyl-8-azabicyclo[3.2.1]octane (Example 110; 134 mg, 0.22 mmol) was dissolved in methanol (10 ml) and hydrochloric acid (2N) (1 ml) and 10% palladium hydroxide (50 mg) added and the mixture hydrogenated at 40 psi overnight. The reaction mixture was then filtered and concentrated in vacuo. The oil was partitioned between saturated sodium hydrogen carbonate solution and dichloromethane and the organics dried (MgSO4) and concentrated in vacuo. The solid was purified by flash column chromatography [5% methanol in dichloromethane]. The hydrochloride salt was made by adding 1 equivalent of hydrogen chloride in diethyl ether to a solution in diethyl ether. The title compound was filtered off and dried in vacuo (32 mg, 26%).

Workup

  1. customhydrogenated at 40 psi overnight
  2. filtrationThe reaction mixture was then filtered
  3. concentrationconcentrated in vacuo
  4. customThe oil was partitioned between saturated sodium hydrogen carbonate solution and dichloromethane
  5. dry with materialthe organics dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe solid was purified by flash column chromatography [5% methanol in dichloromethane]
  8. filtrationThe title compound was filtered off
  9. customdried in vacuo (32 mg, 26%)

Sources & evidence

ORD record
ord-d986d5a760d241499a98c68c66b15863
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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