Chlorosuccinimide → 5-Chloro-2-formamido-4-carboxymethylthiazole

HRID 1858509Notes

Reaction equation

HRID 1858509 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([CH2:9][C:10]([OH:12])=[O:11])[N:8]=1)=[O:2].[Cl:13]N1C(=O)CCC1=O>O1CCCC1>[Cl:13][C:6]1[S:5][C:4]([NH:3][CH:1]=[O:2])=[N:8][C:7]=1[CH2:9][C:10]([OH:12])=[O:11]

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 112868864-Thiazoleacetic acid, 2-(formylamino)-

Product 1

HCID 221243835-Chloro-2-formamido-4-carboxymethylthiazoleYield 29.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-formamido-4-carboxymethylthiazole (2.0 g) in tetrahydrofuran (20 ml) was added N-chlorosuccinimide (1.58 g) and stirred at room temperature overnight. The reaction mixture was added N-chlorosuccinimide (0.5 g) and stirred at the same temperature overnight. The reaction mixture was evaporated under reduced pressure and purified by column chromatography on silica gel (SiO2 =200 ml, chloroform:methanol:acetic acid=20:1:0.1) to give two fractions. The fraction 1 (upper spot by TLC) was purified by column chromatography on silica gel (SiO2 =200 ml, methanol:chloroform=2:8), then the elution was evaporated under reduced pressure. The residue was dissolved in a mixture of water and ethyl acetate, adjusted to pH 8.7 with saturated sodium hydrogencarbonate, and washed with ethyl acetate (×2). The aqueous layer was adjusted to pH 3.0 with 1N-hydrochloric acid, extracted with ethyl acetate (×2), dried over magnesium sulfate, and evaporated under reduced pressure to give white solid which was precipitated from ethyl acetate and N-hexane to give 5-chloro-2-formamido-4-carboxymethylthiazole (694 mg, 29.3%) as a white powder.

Workup

  1. stirringstirred at the same temperature overnight
  2. customThe reaction mixture was evaporated under reduced pressure
  3. custompurified by column chromatography on silica gel (SiO2 =200 ml, chloroform:methanol:acetic acid=20:1:0.1)
  4. customto give two fractions
  5. customThe fraction 1 (upper spot by TLC) was purified by column chromatography on silica gel (SiO2 =200 ml, methanol:chloroform=2:8)
  6. washthe elution
  7. customwas evaporated under reduced pressure
  8. dissolutionThe residue was dissolved in a mixture of water and ethyl acetate
  9. washwashed with ethyl acetate (×2)
  10. extractionextracted with ethyl acetate (×2)
  11. dry with materialdried over magnesium sulfate
  12. customevaporated under reduced pressure
  13. customto give white solid which
  14. customwas precipitated from ethyl acetate and N-hexane

Sources & evidence

ORD record
ord-e44d3bcf56924a26b7afb17460c1552c
Source dataset
uspto-grants-2000_11
Patent number
US06150351

Reaction notes

Loading…