Ethyl chloroformate → 2-Chloro-4-(4-trifluoromethylphenyl)thiazole-5-carboxylic acid ethyl ester

HRID 1667664Notes

Reaction equation

HRID 1667664 reaction equation
[Cl:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[N:6]=1.C([Li])CCC.Cl[C:23]([O:25][CH2:26][CH3:27])=[O:24]>O1CCCC1>[CH2:26]([O:25][C:23]([C:4]1[S:3][C:2]([Cl:1])=[N:6][C:5]=1[C:7]1[CH:8]=[CH:9][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:11][CH:12]=1)=[O:24])[CH3:27]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 214086242-Chloro-4-[4-(trifluoromethyl)phenyl]-1,3-thiazoleHCID 178418339Butyllithium2×

Product 1

HCID 674273002-Chloro-4-(4-trifluoromethylphenyl)thiazole-5-carboxylic acid ethyl esterYield 77.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5.0 g (19.0 mmole) of 2-chloro-4-(4-trifluoromethyl-phenyl)-thiazole and 57 mL of tetrahydrofuran at −78 degrees, was added, over 10 minutes, 9.5 mL of 2.5 M n-butyl lithium in hexanes solution. After 30 minutes, 1.1 mL of 2.5 M n-butyl lithium in hexanes solution was added The mixture was stirred for 2 hours and then 10.63 mL (107.8 mmole) of ethyl chloroformate was added quickly to a rapidly stirring solution. After 15 minutes, the cooling bath was removed and the mixture was stirred at room temperature for 22 minutes. The reaction was quenched by the addition of 75 mL of 1M hydrochloric acid, stirred for 5 minutes and then diluted with 500 mL of ethyl acetate. The ethyl acetate layer was washed twice with 75 mL of water, once with 75 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting dichloromethane-hexanes (gradient 10:90-50:50) to give 4.94 g of 2-chloro-4-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester as a light yellow solid.

Workup

  1. waitAfter 15 minutes
  2. customthe cooling bath was removed
  3. stirringthe mixture was stirred at room temperature for 22 minutes
  4. customThe reaction was quenched by the addition of 75 mL of 1M hydrochloric acid
  5. stirringstirred for 5 minutes
  6. additiondiluted with 500 mL of ethyl acetate
  7. washThe ethyl acetate layer was washed twice with 75 mL of water, once with 75 mL of brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography
  12. washeluting dichloromethane-hexanes (gradient 10:90-50:50)

Sources & evidence

ORD record
ord-757d20cd463c43de9679253ff00b52ab
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

Loading…