1-Phenethylamine, (+)- → HCID 9914377, compound

HRID 1279201Notes

Reaction equation

HRID 1279201 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH:24]=[N:23][N:22]([CH:25]([CH3:29])[C:26](=O)[CH3:27])[C:21]4=[O:30])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:31][C@H:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH2:33]>[Pd].CCCCO.CCCCO.CCCCO.CCCCO.[Ti].S1C=CC=C1>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]([N:20]4[CH:24]=[N:23][N:22]([CH:25]([CH3:29])[CH:26]([NH:33][CH:32]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)[CH3:31])[CH3:27])[C:21]4=[O:30])=[CH:18][CH:19]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 6431891-Phenethylamine, (+)-HCID 151255654-[4-[4-(4-Hydroxyphenyl)piperazin-1-yl]phenyl]-2-(3-oxobutan-2-yl)-1,2,4-triazol-3-one

Product 1

HCID 9914377HCID 9914377, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 521701TetrabutoxytitaniumCatalystHCID 8030ThiopheneSolvent

Procedure

A mixture of (±)-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methyl-2-oxopropyl)-3H-1,2,4-triazol-3-one (0.05 mol) (prepared as described in EP-A-0,228,125 and (+)-(R)-α-methylbenzenemethanamine (0.1 mol) in TBF (500ml) was hydrogenated at 50° C. for 48 hours with Pd/C 10% (10 g) as a catalyst in the presence of titanium(IV) n-butoxide (28.4 g) and thiophene solution (10 ml). The catalyst was filtered off. Pd/C 10% (10 g) was added again. Hydrogenation was continued at 50° C. for 48 hours. After uptake of H2, the mixture was cooled, then the catalyst was filtered off and the filtrate was evaporated. The residue was stirred in CH2Cl2 (500 ml) and H2O (50ml) was added. The mixture was acidified with a concentrated HCl solution, alkalized with a concentrated NH4OH solution and filtered over dicalite. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was triturated in DIPE, filtered off and dried, yielding 23.5 g (91%) of [(R*,R*)(R)+(R*,S*)(R)]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-[2-[( 1 -phenylethyl)amino]-1 -methylpropyl]-3H-1,2,4-triazol-3-one (interm. 1).

Workup

  1. customprepared
  2. filtrationThe catalyst was filtered off
  3. additionPd/C 10% (10 g) was added again
  4. temperatureAfter uptake of H2, the mixture was cooled
  5. filtrationthe catalyst was filtered off
  6. customthe filtrate was evaporated
  7. additionH2O (50ml) was added
  8. filtrationfiltered over dicalite
  9. customThe organic layer was separated
  10. customdried
  11. filtrationfiltered
  12. customthe solvent was evaporated
  13. customThe residue was triturated in DIPE
  14. filtrationfiltered off
  15. customdried

Sources & evidence

ORD record
ord-7fdf5f66689847de9d7f1511c44057ec
Source dataset
uspto-grants-2002_09
Patent number
US06448244B1

Reaction notes

Loading…