Acetic Acid → HCID 68326436, compound

HRID 1400066Notes

Reaction equation

HRID 1400066 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6](=[O:19])[CH:7]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)[CH3:2].[F:21][C:22]([F:32])([F:31])[C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH:26]=O.C(O)(=O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.N1CCCCC1>[CH2:1]([O:3][C:4](=[O:20])/[C:5](/[C:6]([CH:7]1[CH2:8][CH2:9][CH:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:11][CH2:12]1)=[O:19])=[CH:26]\[C:25]1[CH:28]=[CH:29][CH:30]=[C:23]([C:22]([F:21])([F:31])[F:32])[CH:24]=1)[CH3:2]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 679903-(Trifluoromethyl)benzaldehydeHCID 68326348HCID 68326348, compound

Product 1

HCID 68326436HCID 68326436, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 8082PiperidineCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Oxo-3-(4-phenyl-cyclohexyl)-propionic acid ethyl ester (7) (11.56 g, 42.1 mmol), 3-trifluoromethylbenzaldehyde (11 g, 63.15 mmol), glacial acetic acid (7.16 mmol, 0.41 mL) and piperidine (2.1 mmol, 0.21 mL) were dissolved in toluene (250 mL) and heated under Dean and Stark conditions at reflux for 48 hours. The cooled reaction mixtures was diluted with an equal volume of ethyl acetate and washed with 1M aq. HCl and brine. The organics were dried over sodium sulfate, filtered, and evaporated to afford a clear, brown oil. The residue was purified by column chromatography on silica gel (gradient: 0 to 10% tert-butyl methyl ether in cyclohexane) to afford 12.3 g (68%) of (Z)-2-(4-phenyl-cyclohexanecarbonyl)-3-(3-trifluoromethyl-phenyl)-acrylic acid ethyl ester. 1H NMR (400 MHz, 192191), LCMS (method C), Rt=4.77 min, (M+H)+=431.2.

Workup

  1. temperatureheated under Dean and Stark conditions
  2. temperatureat reflux for 48 hours
  3. customThe cooled reaction mixtures
  4. washwashed with 1M aq. HCl and brine
  5. dry with materialThe organics were dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto afford a clear, brown oil
  9. customThe residue was purified by column chromatography on silica gel (gradient: 0 to 10% tert-butyl methyl ether in cyclohexane)

Sources & evidence

ORD record
ord-7d778a17affc46daa89a1164bc2d0159
Source dataset
uspto-grants-2014_12
Patent number
US08906917B2

Reaction notes

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