Hydrochloric Acid → HCID 86586731, compound

HRID 2088188Notes

Reaction equation

HRID 2088188 reaction equation
C([N:8]1[CH:13]2[CH:14]([N:16]3[CH:20]=[N:19][N:18]=[N:17]3)[CH2:15][C:9]1([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH:10]([O:21][CH2:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=1)[CH2:11][CH2:12]2)C1C=CC=CC=1.[ClH:43]>CO.C(OCC)C.[OH-].[Pd+2].[OH-]>[ClH:43].[F:31][C:29]([F:30])([F:32])[C:27]1[CH:28]=[C:23]([CH2:22][O:21][C@@H:10]2[CH2:11][CH2:12][C@@H:13]3[NH:8][C@@:9]2([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:15][C@H:14]3[N:16]2[CH:20]=[N:19][N:18]=[N:17]2)[CH:24]=[C:25]([C:33]([F:34])([F:36])[F:35])[CH:26]=1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid2×HCID 86586733HCID 86586733, compound

Product 1

HCID 86586731HCID 86586731, 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}-1-phenyl-6-(1H-tetrazol-1-yl)-8-azabicyclo[3.2.1]octane. (Example 116; 154 mg, 0.26 mmol) was dissolved in methanol (30 ml) and 2N hydrochloric acid (0.5 ml) and 10% palladium hydroxide (40 mg, 10%) added. The mixture was hydrogenated at 35 psi for 1 hour. The reaction mixture was then filtered and concentrated in vacuo and the oil partitioned between saturated sodium hydrogen carbonate solution and dichloromethane. The organics were collected, dried (MgSO4) and concentrated in vacuo to give an orange foam which was purified by flash column chromatography [7.5% methanol in dichloromethane] then further isolated by thin layer chromatography [7.5% methanol in dichloromethane] to give a clear oil. 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. (25 mg, 18%).

Workup

  1. filtrationThe reaction mixture was then filtered
  2. concentrationconcentrated in vacuo
  3. customthe oil partitioned between saturated sodium hydrogen carbonate solution and dichloromethane
  4. customThe organics were collected
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto give an orange foam which
  8. customwas purified by flash column chromatography [7.5% methanol in dichloromethane]
  9. customthen further isolated by thin layer chromatography [7.5% methanol in dichloromethane]
  10. customto give a clear oil
  11. filtrationthe title compound filtered
  12. customdried in vacuo at 60° C. (25 mg, 18%)

Sources & evidence

ORD record
ord-9e1db19114e94fd2a9f526d18ef90dbe
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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