Hydrogen Bromide → 2,4-Dihydro-4-(4-(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl)-2-((1S)-1-methylpropyl)-3H-1,2,4-triazol-3-one

HRID 1699347Notes

Reaction equation

HRID 1699347 reaction equation
CC1(C)C2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.C[O:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:35]=[CH:34][C:33]([N:36]4[CH:40]=[N:39][N:38]([C@@H:41]([CH3:44])[CH2:42][CH3:43])[C:37]4=[O:45])=[CH:32][CH:31]=3)[CH2:26][CH2:25]2)=[CH:20][CH:19]=1.S([O-])([O-])=O.[Na+].[Na+].Br.C(=O)([O-])[O-].[K+].[K+]>O.ClCCl.C(O)CCC>[OH:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:25][CH2:26][N:27]([C:30]3[CH:31]=[CH:32][C:33]([N:36]4[CH:40]=[N:39][N:38]([C@@H:41]([CH3:44])[CH2:42][CH3:43])[C:37]4=[O:45])=[CH:34][CH:35]=3)[CH2:28][CH2:29]2)=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 11430Potassium CarbonateHCID 24437Sodium SulfiteHCID 131721474(+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate2×

Product 1

HCID 9918902,4-Dihydro-4-(4-(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl)-2-((1S)-1-methylpropyl)-3H-1,2,4-triazol-3-oneYield 77.7%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of 29.4 g of (+)-(S)-2,4-dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptane-1-methanesulfonate (1:2) (intermediate (5)), 2.0 g of sodium sulfite and 151 ml of a hydrobromic acid solution 48% in water was stirred for 5 hours at reflux temperature. The reaction mixture was cooled to room temperature and water was added. The whole was neutralized with potassium carbonate to pH 7 while stirring in a mixture of dichloromethane and 1-butanol (90:10 by volume). The separated organic layer was dried, filtered and evaporated in vacuo. The residue was triturated in methanol. The precipitated product was filtered off and purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 4-methyl-2-pentanone. The product was filtered off and dried, yielding 10.4 g (77.7%) of (+)-(S)-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one; mp. 1 80.6° C.; [α]D20=+4.38° (conc.=1% in methanol) (interm. 7).

Workup

  1. temperatureat reflux temperature
  2. customThe separated organic layer was dried
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue was triturated in methanol
  6. filtrationThe precipitated product was filtered off
  7. custompurified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. customThe residue was crystallized from 4-methyl-2-pentanone
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-355a51a0bc3a48c2af0c2a0f38bd6c24
Source dataset
uspto-grants-2002_02
Patent number
US06346518B1

Reaction notes

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