Triethylamine → 2-Benzyloxy-5-fluoro-(2,2,2-trifluoroethylcarbamoyl)-benzoic acid ethyl ester

HRID 654032Notes

Reaction equation

HRID 654032 reaction equation
[CH2:1]([O:8][C:9]1[C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]([F:21])=[CH:14][C:10]=1[C:11]([OH:13])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH2:26](N(CC)CC)[CH3:27].[F:33][C:34]([F:38])([F:37])[CH2:35][NH2:36]>C(OCC)(=O)C.O1CCCC1>[CH2:26]([O:20][C:18](=[O:19])[C:17]1[CH:16]=[C:15]([F:21])[CH:14]=[C:10]([C:11](=[O:13])[NH:36][CH2:35][C:34]([F:38])([F:37])[F:33])[C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH3:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 24386Thionyl ChlorideHCID 198881632-Benzyloxy-5-fluoroisophthalic acid

Product 1

HCID 150576482-Benzyloxy-5-fluoro-(2,2,2-trifluoroethylcarbamoyl)-benzoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

7.96 g (25 mmol) of 2-benzyloxy-5-fluoroisophthalic acid monethyl ester in dissolved or suspended in 50 ml of dry ethyl acetate, 3.57 g (30 mmol) of thionylchloride is added and stirred for 1 hour at 50° C. The reaction solution is then evaporated to dryness under reduced pressure, the residue is evaporated twice with 50 ml of dichloromethane each and dissolved in 30 ml of dry tetrahydrofuran. This solution is mixed with 3.03 g (30 mmol) of triethylamine and then a solution of 2.97 g (30 mmol) of 2,2,2-trifluoroethylamine in 10 ml of dry tetrahydrofuran is instilled. It is stirred for 5 more hours at room temperature, the reaction solution is concentrated by evaporation to oil under reduced pressure, it is dissolved in 80 ml of ethyl acetate and shaken out twice with 10 ml of 1N hydrochloric acid each and once with 10 ml of water. The organic phase is dried on magnesium sulfate, filtered, concentrated by evaporation and the residue is chromatographed on silica gel 60 (Merck) with ethyl acetate/hexane. 7.25 g (18.15 mmol)=72.6% of the theoretical yield of the compound is obtained as an amorphous solid.

Workup

  1. customThe reaction solution is then evaporated to dryness under reduced pressure
  2. customthe residue is evaporated twice with 50 ml of dichloromethane each and
  3. dissolutiondissolved in 30 ml of dry tetrahydrofuran
  4. stirringIt is stirred for 5 more hours at room temperature
  5. concentrationthe reaction solution is concentrated by evaporation to oil under reduced pressure, it
  6. dissolutionis dissolved in 80 ml of ethyl acetate
  7. stirringshaken out twice with 10 ml of 1N hydrochloric acid each and once with 10 ml of water
  8. customThe organic phase is dried on magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated by evaporation
  11. customthe residue is chromatographed on silica gel 60 (Merck) with ethyl acetate/hexane
  12. custom7.25 g (18.15 mmol)=72.6% of the theoretical yield of the compound is obtained as an amorphous solid

Sources & evidence

ORD record
ord-baa02151973342248d952b108eba2ba8
Source dataset
uspto-grants-1992_07
Patent number
US05130119

Reaction notes

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