Thiophene → HCID 13094234, compound

HRID 1164365Notes

Reaction equation

HRID 1164365 reaction equation
S1C=CC=C1.[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2([C:20]#[N:21])[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]2)=[C:9]([CH3:22])[CH:8]=1.Cl.[C:24]1([C:30]2([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])(=O)C.[Na+].[H][H]>[Pd].C(O)C>[C:20]([C:13]1([C:10]2[CH:11]=[CH:12][C:7]([F:6])=[CH:8][C:9]=2[CH3:22])[CH2:18][CH2:17][CH:16]([N:33]2[CH2:32][CH2:31][C:30]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:35][CH2:34]2)[CH2:15][CH2:14]1)#[N:21]

Participants

8

Reactant 5

HCID 8030ThiopheneHCID 517045Sodium AcetateHCID 205117981-(4-Fluoro-2-methylphenyl)-4-oxocyclohexane-1-carbonitrileHCID 53444519Ethyl 4-phenylpiperidine-4-carboxylate--hydrogen chloride (1/1)HCID 178418361HCID 178418361, compound

Product 1

HCID 13094234HCID 13094234, compoundYield 33.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×

Procedure

To 1 part of a solution of 2 parts of thiophene in 40 parts of ethanol are added 4.7 parts of 1-(4-fluoro-2-methylphenyl)-4-oxocyclohexanecarbonitrile, 5.4 parts of ethyl 4-phenyl-4-piperidinecarboxylate hydrochloride, 2 parts of sodium acetate and 120 parts of ethanol. The whole is hydrogenated at normal pressure and at room temperature with 2 parts of palladium-on-charocal catalyst 10%. After the calculated amount of hydrogen is taken up, the catalyst is filtered off over Hyflo and the filtrate is evaporated. From the residue, the free base is liberated in the conventional manner with ammonium hydroxide and the product is extracted with dichloromethane. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and ethanol (98.5:1.5 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from ethanol, yielding 3 parts (33.4%) of ethyl 1-[4-cyano-4-(4-fluoro-2-methylphenyl)cyclohexyl]-4 -phenyl-4-piperidinecarboxylate; mp. 135.2° C.

Workup

  1. filtrationthe catalyst is filtered off over Hyflo
  2. customthe filtrate is evaporated
  3. extractionthe product is extracted with dichloromethane
  4. customThe extract is dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by column-chromatography over silica gel using
  8. additiona mixture of trichloromethane and ethanol (98.5:1.5 by volume) as eluent
  9. customThe pure fractions are collected
  10. customthe eluent is evaporated
  11. customThe residue is crystallized from ethanol

Sources & evidence

ORD record
ord-b99139ca3569457cb1096477051642aa
Source dataset
uspto-grants-1983_01
Patent number
US04369184

Reaction notes

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