Toluene → 4-Phenyl-2-[acetylthio-methyl]butyric acid

HRID 983674Notes

Reaction equation

HRID 983674 reaction equation
C1(C)C=CC=CC=1.N1CCCCC1.[C:14]1([CH2:20][CH2:21][C:22](=[CH2:26])[C:23]([OH:25])=[O:24])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[S:27]1C=CC=C1CC(O)=O.[CH3:36][CH2:37][O:38]CC>>[C:37]([S:27][CH2:26][CH:22]([CH2:21][CH2:20][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:23]([OH:25])=[O:24])(=[O:38])[CH3:36]

Participants

6

Reactant 5

HCID 1140TolueneHCID 3283Diethyl EtherHCID 8082PiperidineHCID 159702-Thiopheneacetic acid2×HCID 138174112-Methylene-4-phenylbutyric acid

Product 1

HCID 101062544-Phenyl-2-[acetylthio-methyl]butyric acidYield 81%

Conditions

Temperature
5 °C

Procedure

A 250 mL round bottomed flask, fitted with a Teflon magnetic stirring bar and a reflux condenser, was filled with 150 mL of toluene, 0.5 mL piperidine and 8.6 g (49 mmole) of 4-phenyl-2-methylenebutyric acid. Then 4.1 g (54 mmole) of thiolacetic acid was added to the solution and the mixture heated to reflux for 8 hours under nitrogen. 1H-NMR analysis of the reaction mixture indicated some starting material remained. Another 1 g of thiolacetic acid was added and the mixture stirred at reflux for an additional 4 hours. By 1H-NMR, all of the starting material was seen to have reacted. The solution was cooled to 5° C., and 100 mL of ether added to the mixture. The excess thiolacetic acid was removed by extraction (3×50 mL 2% sodium bicarbonate). Then 50 mL of 1N HCl was added to the organic layer and the solution shaken vigorously. The organic layer was separated and dried over MgSO4. The solution was filtered and the solvent removed under reduced pressure. Recovered 10.0 g of product (81% yield).

Workup

  1. customA 250 mL round bottomed flask, fitted with a Teflon magnetic stirring bar and a reflux condenser
  2. temperaturethe mixture heated
  3. temperatureto reflux for 8 hours under nitrogen
  4. temperatureat reflux for an additional 4 hours
  5. customto have reacted
  6. customThe excess thiolacetic acid was removed by extraction (3×50 mL 2% sodium bicarbonate)
  7. additionThen 50 mL of 1N HCl was added to the organic layer
  8. stirringthe solution shaken vigorously
  9. customThe organic layer was separated
  10. dry with materialdried over MgSO4
  11. filtrationThe solution was filtered
  12. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-67aa0b6ec3fc454fbeabea672706ad6a
Source dataset
uspto-grants-2005_03
Patent number
US06864383B2

Reaction notes

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