P-Cresol → HCID 58042518, compound

HRID 2359286Notes

Reaction equation

HRID 2359286 reaction equation
[Cl:1][C:2]1[C:3]([F:12])=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].C(N(CC)CC)C.[CH:20]1[C:25](O)=[CH:24][CH:23]=[C:22]([CH3:27])[CH:21]=1>S(Cl)(Cl)=O.ClCCl.CCCCCCC>[Cl:1][C:2]1[C:3]([F:12])=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([O:9][C:25]1[CH:24]=[CH:23][C:22]([CH3:27])=[CH:21][CH:20]=1)=[O:8]

Participants

7

Reactant 3

HCID 2879P-CresolHCID 8471TriethylamineHCID 148764175-Chloro-2,4-difluorobenzoic acid

Product 1

HCID 58042518HCID 58042518, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8900HeptaneSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
60 °C

Procedure

5-chloro-2,4-difluorobenzoic acid (1.17 g, 0.00608 mol) was dissolved in thionyl dichloride (5.0 mL) and the reaction mixture was heated to 60° C. under nitrogen for 5 hours. The solvent was concentrated in vacuo and the residue was azeotroped twice with dichloromethane (10.0 mL) and once with toluene (10.0 mL). The crude was taken up in dichloromethane (15.0 mL) and cooled to 0° C. with an ice bath under nitrogen. Then N,N-diethylethanamine (1.05 mL, 0.00753 mol) and p-cresol (0.665 g, 0.00615 mol) dissolved in dichloromethane (10.0 mL) were added using a dropping funnel over 10 minutes. The resulting mixture was left to warm up to room temperature for 16 hours. The reaction was concentrated in vacuo and the crude was diluted in ethyl acetate (15.0 mL), washed twice with a saturated aqueous solution of sodium hydrogen carbonate (10.0 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. Resulting crude was taken up in heptane (10.0 mL), put in a sonication bath for 5 minutes and the resulting solid was isolated by filtration. Title compound was obtained as white solid (1.20 g, 0.00425 mol, 70%).

Workup

  1. concentrationThe solvent was concentrated in vacuo
  2. customthe residue was azeotroped twice with dichloromethane (10.0 mL) and once with toluene (10.0 mL)
  3. temperaturecooled to 0° C. with an ice bath under nitrogen
  4. additionwere added
  5. customover 10 minutes
  6. waitThe resulting mixture was left
  7. temperatureto warm up to room temperature for 16 hours
  8. concentrationThe reaction was concentrated in vacuo
  9. additionthe crude was diluted in ethyl acetate (15.0 mL)
  10. washwashed twice with a saturated aqueous solution of sodium hydrogen carbonate (10.0 mL)
  11. dry with materialThe organic layer was then dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customResulting crude
  15. customthe resulting solid was isolated by filtration

Sources & evidence

ORD record
ord-50457fab5d834844b12195927c90d2a3
Source dataset
uspto-grants-2014_04
Patent number
US08685977B2

Reaction notes

Loading…