2,6-Lutidine → 4-Chloro-2,6-bis-trifluoromethyl-nicotinic acid ethyl ester

HRID 255403Notes

Reaction equation

HRID 255403 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:7](O)[CH:6]=[C:5]([C:15]([F:18])([F:17])[F:16])[N:4]=1.N1C(C)=CC=CC=1C.P(Cl)(Cl)([Cl:31])=O>>[F:1][C:2]([F:20])([F:19])[C:3]1[C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:7]([Cl:31])[CH:6]=[C:5]([C:15]([F:18])([F:17])[F:16])[N:4]=1

Participants

4

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 178470034HCID 178470034, compound

Product 1

HCID 138828774-Chloro-2,6-bis-trifluoromethyl-nicotinic acid ethyl esterYield 60%

Procedure

A 500 ml round bottom flask equipped with nitrogen inlet and magnetic stirrer is charged with 40 g (0.132 mol) of product from Example 2 and 24.97 g (0.233 mol) of 2,6-lutidine. To this is slowly added (exothermic) 185 ml (1.98 mol) of phosphorous oxychloride. The flask is fitted with a condenser and the mixture is heated to reflux. After refluxing for 18 hours the material is cooled, concentrated, and the mixture was poured into 150 g of ice slowly. The ice mixture was then poured into 200 ml of 10% HCl (aqueous) and extracted twice with ether. The combined ether layers were washed with 10% NaOH (aqueous), dried (MgSO4), and concentrated in vacuo affording a black oil. The residue was kugelrohr distilled at 67 Pa. The earlier fraction (pot temperature 50° C.) was discarded. The later fraction (pot temperature 85° C.) afforded 25.15 g (60%) of product, nD25 1.4185. Anal. Calc'd. for C10H6Cl1F6N1O2 : C, 37.35; H, 1.88; N, 4.36. Found: C, 37.51; H, 1.74; N, 4.23.

Workup

  1. customA 500 ml round bottom flask equipped with nitrogen inlet and magnetic stirrer
  2. customThe flask is fitted with a condenser
  3. temperaturethe mixture is heated to reflux
  4. temperatureAfter refluxing for 18 hours the material
  5. temperatureis cooled
  6. concentrationconcentrated
  7. additionthe mixture was poured into 150 g of ice slowly
  8. additionThe ice mixture was then poured into 200 ml of 10% HCl (aqueous)
  9. extractionextracted twice with ether
  10. washThe combined ether layers were washed with 10% NaOH (aqueous)
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customaffording a black oil
  14. distillationThe residue was kugelrohr distilled at 67 Pa
  15. customThe earlier fraction (pot temperature 50° C.)

Sources & evidence

ORD record
ord-eda7327199f64a378982bd10c4ece8f0
Source dataset
uspto-grants-1987_10
Patent number
US04698093

Reaction notes

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