Potassium Carbonate → HCID 86618342, compound

HRID 1713058Notes

Reaction equation

HRID 1713058 reaction equation
[NH:1]1[CH2:7][C:5](=[O:6])[NH:4][C:2]1=[S:3].Br[CH:9]([CH2:15][CH3:16])[C:10]([O:12][CH2:13][CH3:14])=[O:11].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:13]([O:12][C:10](=[O:11])[CH2:9][CH2:15][CH2:16][N:4]1[C:5](=[O:6])[CH2:7][NH:1][C:2]1=[S:3])[CH3:14]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 79039Butanoic acid, 2-bromo-, ethyl ester2×HCID 12740302-Thiohydantoin

Product 1

HCID 86618342HCID 86618342, compoundYield 112.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

As depicted in Scheme 40 below, 2-thiohydantoin (1.4 grams, 12 mmol) was dissolved in DMF (50 ml) and ethyl bromobutyrate (0.48 ml, 3.4 mmol, 0.28 molequivalents) and K2CO3 (2.07 grams, 15 mmol, 1.5 molequivalents) were added thereto. The mixture was stirred at room temperature for 2 hours and then additional ethyl bromobutyrate (0.48 ml, 3.4 mmol, 0.28 molequivalents) was added and the reaction mixture was stirred for 16 hours until all starting material was consumed, as indicated by TLC. Thereafter methylene chloride was added followed by addition of water, the organic phase was extracted, the aqueous layer was washed 5 times with methylene chloride and the combined organic phase was washed 10 times in order to remove residual DMF, dried over Na2SO4 and the solvent was evaporated under reduced pressure to afford a black oil. The crude product was purified by liquid chromatography using silica gel 60 (230-400 mesh) and a 6:4 hexane:methylene chloride mixture, a 5.8:4:0.2 hexane:methylene chloride:ethyl acetate mixture, a 5.5:4:0.5 hexane:methylene chloride:ethyl acetate mixture, a 5:4:1 hexane:methylene chloride:ethyl acetate mixture, a 4:4:2 hexane:methylene chloride:ethyl acetate mixture and a 3:4:3 hexane:methylene chloride:ethyl acetate mixture, sequentially, as eluents. Pure 4-(5-oxo-2-thioxo-imidazolidin-1-yl)-butyric acid ethyl ester (884 mg, 32% yield) was obtained as a yellowish oil.

Workup

  1. stirringthe reaction mixture was stirred for 16 hours until all starting material
  2. customwas consumed
  3. additionThereafter methylene chloride was added
  4. additionfollowed by addition of water
  5. extractionthe organic phase was extracted
  6. washthe aqueous layer was washed 5 times with methylene chloride
  7. washthe combined organic phase was washed 10 times in order
  8. customto remove residual DMF
  9. dry with materialdried over Na2SO4
  10. customthe solvent was evaporated under reduced pressure
  11. customto afford a black oil
  12. customThe crude product was purified by liquid chromatography

Sources & evidence

ORD record
ord-53ea5e7537b34aeb9d4e0f4de92034ed
Source dataset
uspto-grants-2010_09
Patent number
US07795255B2

Reaction notes

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