Trifluoroacetic acid → HCID 68426366, compound

HRID 642292Notes

Reaction equation

HRID 642292 reaction equation
C([O:3][C:4]([C:6]1[S:10][C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[N:8][C:7]=1[CH2:18][N:19](C(OC(C)(C)C)=O)[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=O)C.CC([O-])(C)C.[K+].C(O)(C(F)(F)F)=O>C1COCC1.ClCCl>[CH2:24]([O:23][C:21]([C:20]1[N:19]=[CH:18][C:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[S:10][C:6]=2[C:4]=1[OH:3])=[O:22])[CH3:25]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 23665647Potassium tert-butoxideHCID 68427417HCID 68427417, compound

Product 1

HCID 68426366HCID 68426366, compoundYield 0%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A mixture of 4-[(tert-butoxycarbonyl-ethoxycarbonylmethyl-amino)-methyl]-2-(4-chloro-phenyl)-thiazole-5-carboxylic acid ethyl ester (964 mg, 2.00 mol) in THF (7.2 mL) was added drop wise a solution of 1 M KOtBu in THF (2.8 mL, 0.02 mmol) at −78° C. The red solution was stirred at −78° C. for 20 min, warmed to room temperature and stirred at that temperature for two hours before it was quenched with water, extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a yellow oil. It was dissolved in dichloromethane (4 mL) and TFA (1 mL) was added. The mixture was stirred at room temperature for 1 h before it was concentrated in vacuo. It was redissolved in dichloromethane, triethylamine (1.4 mL) was added. The mixture was stirred under air overnight before it was partitioned between ethyl acetate and water, the organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and dichloromethane to give the title compound as a white solid (59 mg): MS: (+) m/z 335.0 M+1).

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred at that temperature for two hours before it
  3. customwas quenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customto give a yellow oil
  9. stirringThe mixture was stirred at room temperature for 1 h before it
  10. concentrationwas concentrated in vacuo
  11. dissolutionIt was redissolved in dichloromethane
  12. additiontriethylamine (1.4 mL) was added
  13. stirringThe mixture was stirred under air overnight before it
  14. customwas partitioned between ethyl acetate and water
  15. washthe organic layer was washed with brine
  16. dry with materialdried over anhydrous sodium sulfate
  17. concentrationconcentrated in vacuo
  18. customThe residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and dichloromethane

Sources & evidence

ORD record
ord-fc28baed666a4870b3912df496736f8e
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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