Dimethylformamide → 6-(Trifluoromethyl)imidazo[2,1-b][1,3]thiazole-5-carboxylic acid

HRID 560304Notes

Reaction equation

HRID 560304 reaction equation
O=P(Cl)(Cl)Cl.CN([CH:9]=[O:10])C.[F:11][C:12]([F:22])([F:21])[C:13]1[N:14]=[C:15]2[N:19]([CH:20]=1)[CH:18]=[CH:17][S:16]2.Cl([O-])=[O:24].[Na+].O.O.P([O-])(O)(O)=O.[Na+]>C(Cl)(Cl)Cl.C(O)(C)(C)C.O>[F:22][C:12]([F:21])([F:11])[C:13]1[N:14]=[C:15]2[N:19]([C:20]=1[C:9]([OH:10])=[O:24])[CH:18]=[CH:17][S:16]2

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 110846966-(Trifluoromethyl)imidazo[2,1-b]thiazoleHCID 23668197Sodium ChloriteHCID 23673460Sodium Phosphate, Monobasic, Dihydrate

Product 1

HCID 574371426-(Trifluoromethyl)imidazo[2,1-b][1,3]thiazole-5-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolvent2×HCID 6386tert-ButanolSolvent

Procedure

At 0° C. POCl3 (17.1 mmol) is added dropwise to a solution of DMF (20.6 mmol) in chloroform (5.0 mL). A solution of 6-trifluoromethyl-imidazo[2,1-b]thiazole (3.17 mmol) in chloroform (15 mL) is added dropwise at 0° C. and the mixture is stirred for 3 h at RT. After heating for 2.5 d to reflux the mixture is poured into ice, extracted three times with DCM, dried over MgSO4 and concentrated under reduced pressure. DCM is added, the obtained precipitate is filtered off and the filtrate is concentrated in vacuo to give a crude product which is dissolved in tert.-butanol (19.5 mL). A solution of sodium chlorite (23.0 mmol) and sodium dihydrogen phosphate dihydrate (17.6 mmol) in water (19.5 mL) is added dropwise and the mixture is stirred for 90 min at RT. The solvents are partially removed in vacuo and the obtained precipitate is filtered off to give the desired product as a white solid. LC-MS: tR=0.73 min; [M+H]+=237.2.

Workup

  1. customAt 0° C
  2. temperatureAfter heating for 2.5 d
  3. temperatureto reflux the mixture
  4. additionis poured into ice
  5. extractionextracted three times with DCM
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. additionDCM is added
  9. filtrationthe obtained precipitate is filtered off
  10. concentrationthe filtrate is concentrated in vacuo
  11. customto give a crude product which
  12. stirringthe mixture is stirred for 90 min at RT
  13. customThe solvents are partially removed in vacuo
  14. filtrationthe obtained precipitate is filtered off

Sources & evidence

ORD record
ord-4dee882d0977447c8fcf724296bc4c07
Source dataset
uspto-grants-2011_11
Patent number
US08063099B2

Reaction notes

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