p-Toluenesulfonic acid → HCID 10316741, compound

HRID 1029540Notes

Reaction equation

HRID 1029540 reaction equation
[OH-].[K+].[CH3:3][C:4]([C:7]1[CH:8]=[C:9]([CH2:18][CH2:19][C:20]([NH:22][NH2:23])=O)[CH:10]=[C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:12]=1[OH:13])([CH3:6])[CH3:5].IC.C1(C)C=C[C:29]([S:32](O)(=O)=O)=CC=1.[C:37](=S)=[S:38]>CO.CCOCC.C1(C)C=CC=CC=1>[CH3:3][C:4]([C:7]1[CH:8]=[C:9]([CH2:18][CH2:19][C:20]2[S:38][C:37]([S:32][CH3:29])=[N:23][N:22]=2)[CH:10]=[C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:12]=1[OH:13])([CH3:6])[CH3:5]

Participants

9

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 14797Potassium HydroxideHCID 648653,5-Di-tert-butyl-4-hydroxyhydrocinnamic acid hydrazide

Product 1

HCID 10316741HCID 10316741, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

Potassium hydroxide (0.22 g, 3.3 mM) is added to a 0° C. solution of 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzenepropanoic acid hydrazide (1.0 g, 3.4 mM) and carbon disulfide (0.22 mL, 7.2 mM) in methanol (36 mL). The reaction mixture is stirred at 0° C. for 2 hours then at room temperature for 4 hours. Iodomethane (0.21 mL, 3.4 mM) is added and stirring is continued overnight. The reaction is diluted with ether and washed twice with water, once with a saturated solution of sodium bicarbonate, and once with brine. Drying the organic phase over magnesium sulfate and evaporation gives 1.2 g of crude intermediate which is dissolved in toluene (20 mL). p-Toluenesulfonic acid (0.72 g, 3.8 mM) is added to the solution and the reaction is heated at reflux for 1.5 hours. The reaction solution is cooled and filtered. The filtrate is diluted with ether and washed twice with water, once with a saturated solution of sodium bicarbonate, and once with brine. Drying the organic phase over magnesium sulfate and evaporation gives a crude product which is chromatographed on silica gel eluting with 1:9 then 2:8 ethyl acetate:hexane yielding 0.29 g (25%) of a white solid which is 2,6-bis(1,1-dimethylethyl)-4-[2-[5-(methylthio)-1,3,4-thiadiazol-2-yl]ethyl]phenol; mp 135°-139° C.

Workup

  1. waitat room temperature for 4 hours
  2. stirringstirring
  3. waitis continued overnight
  4. washwashed twice with water, once with a saturated solution of sodium bicarbonate
  5. customDrying the organic phase
  6. customover magnesium sulfate and evaporation
  7. customgives 1.2 g of crude intermediate which
  8. temperaturethe reaction is heated
  9. temperatureat reflux for 1.5 hours
  10. temperatureThe reaction solution is cooled
  11. filtrationfiltered
  12. additionThe filtrate is diluted with ether
  13. washwashed twice with water, once with a saturated solution of sodium bicarbonate
  14. customDrying the organic phase
  15. customover magnesium sulfate and evaporation

Sources & evidence

ORD record
ord-6eb2d8c11402414689748d90e0f0182a
Source dataset
uspto-grants-1992_04
Patent number
US05102897

Reaction notes

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