Thiophene → HCID 86619164, compound

HRID 991369Notes

Reaction equation

HRID 991369 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH:9]1[CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=1)=[O:7].[CH3:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[C:38]=1[NH:44][C:45](=[O:53])[CH2:46][N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.S1C=CC=C1>CC(O)C.[Pt].CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[F:32][C:30]([F:31])([F:33])[C:28]1[CH:27]=[C:5]([CH:4]=[C:3]([C:2]([F:35])([F:1])[F:34])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:50]2[CH2:51][CH2:52][N:47]([CH2:46][C:45]([NH:44][C:38]3[C:39]([CH3:43])=[CH:40][CH:41]=[CH:42][C:37]=3[CH3:36])=[O:53])[CH2:48][CH2:49]2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[C:18]([F:26])[CH:17]=1)=[O:7].[F:32][C:30]([F:31])([F:33])[C:28]1[CH:27]=[C:5]([CH:4]=[C:3]([C:2]([F:35])([F:1])[F:34])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([N:50]2[CH2:51][CH2:52][N:47]([CH2:46][C:45]([NH:44][C:38]3[C:39]([CH3:43])=[CH:40][CH:41]=[CH:42][C:37]=3[CH3:36])=[O:53])[CH2:48][CH2:49]2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[C:18]([F:26])[CH:17]=1)=[O:7]

Participants

8

Reactant 3

HCID 8030ThiopheneHCID 2608606Cvt-2738HCID 18630841HCID 18630841, compound

Product 2

HCID 86619163HCID 86619163, compoundYield 10%HCID 86619164HCID 86619164, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 23939PlatinumCatalystHCID 3776IsopropanolSolvent

Procedure

A mixture of (±)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[[3-fluoro-5-(trifluoromethyl) phenyl]methyl]-4-piperidinone (0.01 mol) and N-(2,6-dimethylphenyl)-1-piperazine-acetamide (0.01 mol) in 2-propanol (150 ml) was hydrogenated at 50° C. with platinum on activated carbon (55), 2 g) as a catalyst in the presence of titanium(IV)isopropoxide (2.84 g) and thiophene solution (1 ml). After uptake of hydrogen, the catalyst was filtered off and the filtrate was evaporated. The residue was taken up in CH2Cl2 and H2O. The organic layer was separated, washed several times with H2O, dried, filtered over dicalite and the solvent was evaporated. This fraction was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 98/2). Two pure factions were collected and their solvents were evaporated. The residue was dried, yielding 0.72 g (10%) of (±)-cis-4-[1-[3,5-bis (trifluoromethyl)benzoyl]-2-[[3fluoro-5-(trifluoromethyl) phenyl]methyl]-4-piperidinyl]-N—(2,6-dimethylphenyl)-1-piperazineacetamide (compound 140 ) and 0.88 g (12%) of (±)-trans-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-[[3-fluoro-5-(trifluoro-methyl) phenyl]methyl]-4-piperidinyl]-N—(2,6-dimethylphenyl)-1-piperazineacetamide (compound 141).

Workup

  1. filtrationAfter uptake of hydrogen, the catalyst was filtered off
  2. customthe filtrate was evaporated
  3. customThe organic layer was separated
  4. washwashed several times with H2O
  5. customdried
  6. filtrationfiltered over dicalite
  7. customthe solvent was evaporated
  8. customThis fraction was purified by HPLC over silica gel (eluent: CH2Cl2/CH3OH 98/2)
  9. customTwo pure factions were collected
  10. customtheir solvents were evaporated
  11. customThe residue was dried

Sources & evidence

ORD record
ord-8884a82ccd264e8ba4eb91024956d4c8
Source dataset
uspto-grants-2002_10
Patent number
USRE037886E1

Reaction notes

Loading…