Ethyl diazoacetate → HCID 86603352, compound

HRID 857859Notes

Reaction equation

HRID 857859 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[N+:15](=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N-:16]>S(Cl)(Cl)=O>[CH2:21]([O:20][C:18](=[O:19])[C:17](=[N+:15]=[N-:16])[C:4]([C:3]1[C:2]([Cl:1])=[N:10][C:9]([C:11]([F:14])([F:13])[F:12])=[CH:8][CH:7]=1)=[O:6])[CH3:22]

Participants

4

Reactant 2

HCID 12192Ethyl diazoacetateHCID 27782102-Chloro-6-(trifluoromethyl)nicotinic acid

Product 1

HCID 86603352HCID 86603352, compoundYield 96.1%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

2-Chloro-6-trifluoromethylnicotinic acid (10.0 g, 44.3 mmol) was suspended in thionyl chloride (85 ml) and heated under reflux for 2 h. The mixture was allowed to cool to ambient temperature, the solvent was removed in vacuo, toluene (50 ml) was added and the solution concentrated to afford a brown residue. This residue was cooled to −10° C. before ethyl diazoacetate (12.7 g, 110 mmol) was added dropwise over 30 min (maintaining the internal temperature below −5° C.). On complete addition the mixture was allowed to stir at 0° C. for 1 h then heated at 55° C. for 18 h. The mixture was allowed to cool to ambient temperature then evaporated. The residue was purified by dry flash chromatography on silica eluting with isohexane on a gradient of ethyl acetate (10–30%). Collecting the appropriate fractions gave 3-(2-chloro-6-trifluoromethyl-pyridin-3-yl)-2-diazo-3-oxo-propionic acid ethyl ester (13.7 g, 96%) as a yellow oil: δH (400 MHz, CDCl3) 1.17 (3H, t, J7), 4.15 (2H, q, J7), 7.68 (1H, d, J8), 7.78 (1H, d, J8), CHN2 absent.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2 h
  3. customthe solvent was removed in vacuo, toluene (50 ml)
  4. additionwas added
  5. concentrationthe solution concentrated
  6. customto afford a brown residue
  7. additionwas added dropwise over 30 min (
  8. temperaturemaintaining the internal temperature below −5° C.)
  9. additionOn complete addition the mixture
  10. temperaturethen heated at 55° C. for 18 h
  11. temperatureto cool to ambient temperature
  12. customthen evaporated
  13. customThe residue was purified
  14. dry with materialby dry flash chromatography on silica eluting with isohexane on a gradient of ethyl acetate (10–30%)
  15. customCollecting the appropriate fractions

Sources & evidence

ORD record
ord-e0a048f47be94cbf8aa86b47c840a1ef
Source dataset
uspto-grants-2006_12
Patent number
US07148222B2

Reaction notes

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