Sodium Bicarbonate → (4S,9aS)-4-benzhydryl-8-benzyloxycarbonyl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine

HRID 1006370Notes

Reaction equation

HRID 1006370 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]([C:16]([F:19])([F:18])[F:17])=[N:14][N:13]=[N:12]2)=[CH:7][C:4]=1[CH:5]=O.Cl.Cl.[CH:22]([C@@H:35]1[N:40]2[CH2:41][CH2:42][N:43]([C:45]([O:47][CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:46])[CH2:44][C@@H:39]2[CH2:38][NH:37][CH2:36]1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[Na].C(=O)([O-])O.[Na+]>ClCCl>[CH:22]([C@@H:35]1[N:40]2[CH2:41][CH2:42][N:43]([C:45]([O:47][CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:46])[CH2:44][C@@H:39]2[CH2:38][N:37]([CH2:5][C:4]2[CH:7]=[C:8]([N:11]3[C:15]([C:16]([F:19])([F:18])[F:17])=[N:14][N:13]=[N:12]3)[CH:9]=[CH:10][C:3]=2[O:2][CH3:1])[CH2:36]1)([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5360545SodiumHCID 113916182-Methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]benzaldehydeHCID 69818941(4S,9aS)-4-benzhydryl-8-(benzyloxycarbonyl)octahydro-2H-pyrazino[1,2-a]pyrazine dihydrochloride

Product 1

HCID 69819381(4S,9aS)-4-benzhydryl-8-benzyloxycarbonyl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazineYield 72.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzaldehyde (582 mg) and (4S,9aS)-4-benzhydryl-8-(benzyloxycarbonyl)octahydro-2H-pyrazino[1,2-a]pyrazine dihydrochloride (1.0 g) in dichloromethane (10 ml) was added portionwise sodium tritacetoxyborohydride (824 mg) under ice-cooling, and then it was stirred at room temperature for 90 minutes. The mixture was poured into aqueous sodium hydrogen carbonate and extracted with dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, and evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (23 g) using a mixed solvent of hexane and ethyl acetate (2:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (4S,9aS)-4-benzhydryl-8-benzyloxycarbonyl-2-[2-methoxy-5-[5-(trifluoromethyl)-1H-tetrazol-1-yl]benzyl]octahydro-2H-pyrazino[1,2-a]pyrazine (0.98 g) as a colorless foam.

Workup

  1. temperaturecooling
  2. extractionextracted with dichloromethane
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe resulting residue was purified by column chromatography on silica gel (23 g)
  7. additionThe fractions containing the objective compound
  8. customwere collected
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-d7d7816e3ea8472183add20abd74244e
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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