p-Toluenesulfonic acid → Ethyl 2-cyclopropylthiazole-4-carboxylate

HRID 471115

Reaction equation

HRID 471115 reaction equation
[CH:1]1([C:4]([NH:6][CH:7]([CH2:13][SH:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=O)[CH2:3][CH2:2]1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH:1]1([C:4]2[S:14][CH:13]=[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 57989028Ethyl 2-(cyclopropanecarboxamido)-3-mercaptopropanoate

Product 1

HCID 18771956Ethyl 2-cyclopropylthiazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of ethyl 2-(cyclopropanecarboxamido)-3-mercaptopropanoate (example 57, step a) (5 g) and tosic acid (0.875 g) in toluene (100 mL) was heated at reflux under Dean and Stark conditions overnight. The reaction was allowed to cool and the toluene solution was washed with saturated sodium hydrogen carbonate solution (3×100 mL) dried over sodium sulphate, filtered and evaporated. The resulting brown gum was redissolved in acetonitrile (100 mL). Manganese dioxide (40 g) was added and the mixture heated at reflux overnight. The reaction was filtered through Celite and the filter pad washed with MeCN (3×100 mL). The combined filtrate and washings were evaporated and the residue purified by silica gel chromatography eluting with 9:1 to 4:1 isohexane:ethyl acetate gradient. The fractions containing product were combined and evaporated to give the subtitled compound as a clear oil. Yield 0.15 g.

Workup

  1. temperatureat reflux under Dean and Stark conditions overnight
  2. temperatureto cool
  3. washthe toluene solution was washed with saturated sodium hydrogen carbonate solution (3×100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe resulting brown gum was redissolved in acetonitrile (100 mL)
  8. additionManganese dioxide (40 g) was added
  9. temperaturethe mixture heated
  10. temperatureat reflux overnight
  11. filtrationThe reaction was filtered through Celite
  12. washthe filter pad washed with MeCN (3×100 mL)
  13. customThe combined filtrate and washings were evaporated
  14. customthe residue purified by silica gel chromatography
  15. washeluting with 9:1 to 4:1 isohexane
  16. additionThe fractions containing product
  17. customevaporated

Sources & evidence

ORD record
ord-20edbe6bf1e447d69b3e3d47fb3f047f
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Linked notes

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