Thiophene → HCID 86619164, compound

HRID 1060200Notes

Reaction equation

HRID 1060200 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 50C with platinum on activated carbon (5%; 2 g) as a catalyst in the presence of titanium(IV)isopropoxide (2.84 g) and thiophene solution (1 ml). After uptake of hyrogen, 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 fractions 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-[[3-fluoro-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 hyrogen, 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 fractions were collected
  10. customtheir solvents were evaporated
  11. customThe residue was dried

Sources & evidence

ORD record
ord-f77b2af0e8d546b3b34d3dcb24305db5
Source dataset
uspto-grants-2003_02
Patent number
US06521621B1

Reaction notes

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