Methanol → 4-(3-(4-Hydroxybutyl)-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)-2-(trifluoromethyl)benzonitrile

HRID 1872325Notes

Reaction equation

HRID 1872325 reaction equation
CN(C)C=O.[CH3:6][C:7]1([CH3:26])[C:11](=[O:12])[N:10]([C:13]2[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[C:15]([C:21]([F:24])([F:23])[F:22])[CH:14]=2)[C:9](=[O:25])[NH:8]1.C([O:30][CH2:31][CH2:32][CH2:33][CH2:34]Br)(=O)C.CO>O>[CH3:6][C:7]1([CH3:26])[C:11](=[O:12])[N:10]([C:13]2[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[C:15]([C:21]([F:24])([F:22])[F:23])[CH:14]=2)[C:9](=[O:25])[N:8]1[CH2:34][CH2:33][CH2:32][CH2:31][OH:30]

Participants

6

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 784911-Butanol, 4-bromo-, 1-acetateHCID 111622854-(4,4-Dimethyl-2,5-dioxoimidazolidin-1-yl)-2-trifluoromethylbenzonitrile

Product 1

HCID 1329814-(3-(4-Hydroxybutyl)-4,4-dimethyl-2,5-dioxo-1-imidazolidinyl)-2-(trifluoromethyl)benzonitrileYield 89.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
30 °C

Procedure

300 ml of dimethylformamide and 100 g of the product of Example 3 are introduced at 20°/22° C. and the reaction medium is maintained under agitation at this temperature for approximately 5 minutes then 98.5 g of 4-bromobutyl acetate then 20 g of soda are added and the whole is maintained under agitation and under a nitrogen atmosphere at +20°/+22° C. for approximately 22 hours. While maintaining agitation, at this temperature, 20 g of soda is added then over approximately 5 minutes 400 ml of methanol is added and the whole is maintained in this way for 1 hour. While leaving the temperature to rise, 500 ml of demineralized water at +20° C. is introduced under agitation, then the reaction medium is placed under agitation, 500 ml of demineralized water is added at +20° C. and the whole is maintained under agitation for 1 hour at 25°/30° C., then cooled down under agitation to +0°/+5° C., and maintained for 2 hours, followed by separating, washing with 4×100 ml of demineralized water and drying. Purification is carried out by adding 696 ml of methylene chloride at 20°/22° C. and washing with 3×232 ml of demineralized water then drying, 5.8 g of supra black is added, the medium is maintained under agitation at 20°±2° C. for 2 hours followed by filtering and rinsing with 2×116 ml of methylene chloride. After concentrating under agitation, 116 ml of denat. ethanol toluene is added at 20° C. then 174 ml of demineralized water is added. The reaction medium is cooled down under agitation to 20°/22° C., maintained under agiatation for 2 hours at this temperature then cooled down to 0°±2° C. and maintained for 1 hour under these conditions, followed by separating, washing with 2×58 ml of ethanol with 50% water at 0°/+2° C. and drying. In this way 111.5 g of expected product (white powder) is obtained. M.p.=102° C.

Workup

  1. temperaturethe reaction medium is maintained under agitation at this temperature for approximately 5 minutes
  2. temperaturethe whole is maintained under agitation and under a nitrogen atmosphere at +20°/+22° C. for approximately 22 hours
  3. temperatureWhile maintaining agitation
  4. additionat this temperature, 20 g of soda is added
  5. temperaturethe whole is maintained in this way for 1 hour
  6. customWhile leaving the temperature
  7. additionis added at +20° C.
  8. temperaturecooled down under agitation to +0°/+5° C.
  9. temperaturemaintained for 2 hours
  10. customby separating
  11. washwashing with 4×100 ml of demineralized water
  12. customdrying
  13. customPurification
  14. additionby adding 696 ml of methylene chloride at 20°/22° C.
  15. washwashing with 3×232 ml of demineralized water
  16. customthen drying
  17. addition5.8 g of supra black is added
  18. temperaturethe medium is maintained under agitation at 20°±2° C. for 2 hours
  19. filtrationby filtering
  20. washrinsing with 2×116 ml of methylene chloride
  21. concentrationAfter concentrating under agitation, 116 ml of denat
  22. additionethanol toluene is added at 20° C.
  23. addition174 ml of demineralized water is added
  24. temperatureThe reaction medium is cooled down under agitation to 20°/22° C.
  25. temperaturemaintained under agiatation for 2 hours at this temperature
  26. temperaturethen cooled down to 0°±2° C.
  27. temperaturemaintained for 1 hour under these conditions
  28. customby separating
  29. washwashing with 2×58 ml of ethanol with 50% water at 0°/+2° C.
  30. customdrying

Sources & evidence

ORD record
ord-ac8cef936da94c1e9aeb65ea71302461
Source dataset
uspto-grants-2000_08
Patent number
US06107488

Reaction notes

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