Hydrochloric Acid → (4S,9aR)-4-benzhydryl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine trihydrochloride

HRID 1006371Notes

Reaction equation

HRID 1006371 reaction equation
[CH:1]([C@@H:14]1[N:19]2[CH2:20][CH2:21][N:22](C(OCC3C=CC=CC=3)=O)[CH2:23][C@@H:18]2[CH2:17][N:16]([CH2:34][C:35]2[CH:40]=[C:39]([N:41]3[C:45]([C:46]([F:49])([F:48])[F:47])=[N:44][N:43]=[N:42]3)[CH:38]=[CH:37][C:36]=2[O:50][CH3:51])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[ClH:59]>O1CCCC1.ClCCl.C(OCC)(=O)C.[Pd]>[ClH:59].[ClH:59].[ClH:59].[CH:1]([C@@H:14]1[N:19]2[CH2:20][CH2:21][NH:22][CH2:23][C@@H:18]2[CH2:17][N:16]([CH2:34][C:35]2[CH:40]=[C:39]([N:41]3[C:45]([C:46]([F:49])([F:48])[F:47])=[N:44][N:43]=[N:42]3)[CH:38]=[CH:37][C:36]=2[O:50][CH3:51])[CH2:15]1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 69819381(4S,9aS)-4-benzhydryl-8-benzyloxycarbonyl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine

Product 1

HCID 86589654(4S,9aR)-4-benzhydryl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine trihydrochloride

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4S,9aS)-4-Benzhydryl-8-benzyloxycarbonyl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine (187 mg) was dissolved in tetrahydrofuran (2 ml), and triethylamine (0.0747 ml) was added to it at room temperature. The solution was hydrogenated over 10% palladium-charcoal (50% wet, 40 mg) at room temperature under atmospheric pressure for 2 hours. After removal of the catalyst by filtration, the filtrate was evaporated under reduced pressure to give colorless syrup. The resulting residue was purified by column chromatography on silica gel (7 g) using a mixed solvent of dichloromethane and methanol (10:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give a syrup. To a solution of the syrup in dichloromethane (2 ml) was added a solution of 4N hydrogen chloride in ethyl acetate (0.050 ml), and triturated with diisopropyl ether. The precipitate was collected by filtration and dried under reduced pressure for 5 hours at 40° C. to give (4S,9aR)-4-benzhydryl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine trihydrochloride (154 mg) as a colorless powder.

Workup

  1. customAfter removal of the catalyst
  2. filtrationby filtration
  3. customthe filtrate was evaporated under reduced pressure
  4. customto give colorless syrup
  5. customThe resulting residue was purified by column chromatography on silica gel (7 g)
  6. additionThe fractions containing the objective compound
  7. customwere collected
  8. customevaporated under reduced pressure
  9. customto give a syrup
  10. customtriturated with diisopropyl ether
  11. filtrationThe precipitate was collected by filtration
  12. customdried under reduced pressure for 5 hours at 40° C.

Sources & evidence

ORD record
ord-01c4229c910e499f86c957c00806117c
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

Loading…