Water → HCID 13094214, compound

HRID 1164366Notes

Reaction equation

HRID 1164366 reaction equation
[C:1]([C:3]1([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH2:8][CH2:7][CH:6]([N:9]2[CH2:14][CH2:13][C:12]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([C:15]([O:17]CC)=[O:16])[CH2:11][CH2:10]2)[CH2:5][CH2:4]1)#[N:2].[OH-].[K+].O>CC(O)C>[C:1]([C:3]1([C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[CH2:8][CH2:7][CH:6]([N:9]2[CH2:14][CH2:13][C:12]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)([C:15]([OH:17])=[O:16])[CH2:11][CH2:10]2)[CH2:5][CH2:4]1)#[N:2]

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 13094235HCID 13094235, compound

Product 1

HCID 13094214HCID 13094214, compoundYield 66.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 10.9 parts of ethyl 1-[4-cyano-4-(4-fluorophenyl)-1-cyclohexyl]-4-phenyl-4-piperidinecarboxylate, 11.2 parts of potassium hydroxide, 50 parts of water and 96 parts of 2-propanol is stirred and refluxed for 4 hours. The reaction mixture is filtered hot over Hyflo and the filtrate is poured onto 300 parts of water. The whole is neutralized with acetic acid to pH 6-7. The precipitated product is filtered off, washed three times with water and converted into the hydrochloride salt in ethanol and 2-propanol. The salt is filtered off and suspended in a solution of 1.4 parts of potassium hydroxide in 150 parts of water. The free base is extracted four times with 70 parts of 1,1'-oxybisethane. The aqueous phase is separated and stirred for a while on a rotavapor to remove all traces of 1,1'-oxybisethane. The clear aqueous phase is acidified with a 10% acetic acid solution to pH 6. The precipitated product is filtered off, washed with water and dried overnight at about 105° C., yielding 5.4 parts (66.4%) of 1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-4-phenyl-4-piperidinecarboxylic acid; mp. 281.1° C.

Workup

  1. temperaturerefluxed for 4 hours
  2. filtrationThe reaction mixture is filtered hot over Hyflo
  3. additionthe filtrate is poured onto 300 parts of water
  4. filtrationThe precipitated product is filtered off
  5. washwashed three times with water
  6. filtrationThe salt is filtered off
  7. extractionThe free base is extracted four times with 70 parts of 1,1'-oxybisethane
  8. customThe aqueous phase is separated
  9. stirringstirred for a while on a rotavapor
  10. customto remove all traces of 1,1'-oxybisethane
  11. filtrationThe precipitated product is filtered off
  12. washwashed with water
  13. customdried overnight at about 105° C.

Sources & evidence

ORD record
ord-12ee20fc45994b0798bc00955382c39b
Source dataset
uspto-grants-1983_01
Patent number
US04369184

Reaction notes

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