Hydrochloric Acid → Chf-5074

HRID 2172651Notes

Reaction equation

HRID 2172651 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3([C:18]#N)[CH2:17][CH2:16]3)=[CH:11][C:10]=2[F:20])[CH:5]=[CH:6][C:7]=1[Cl:8].[OH-:21].[K+].Cl.C[OH:25]>O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3([C:18]([OH:25])=[O:21])[CH2:17][CH2:16]3)=[CH:11][C:10]=2[F:20])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14797Potassium HydroxideHCID 44544164HCID 44544164, compound

Product 1

HCID 9996409Chf-5074

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
2.5 °C

Procedure

1-(3′,4′-dichloro-2-fluoro[1,1′-biphenyl]-4-yl)-cyclopropanenitrile (14.3 g, 0.047 mol) is dissolved in a mixture of methanol (143 ml) and water (71.5 ml), potassium hydroxide (35.1 g, 0.563 mol) is added portionwise, and the mixture is refluxed for 48 hours. The reaction mixture is cooled and poured into a solution of aqueous hydrogen chloride 36% (57 ml) in water (57 ml) at 20-25° C. The suspension is stirred and filtered; the solid is repeatedly washed with water and dried at 40° C. under vacuum. The crude product is dissolved in refluxing 2-propanol (178 ml), the solution is mixed with activated carbon (0.3 g), stirred at reflux and filtered, concentrated and mixed with n-heptane (116 ml). The hot solution is cooled to 0 to 5° C. and the crystallized solid is filtered, washed with 2-propanol and dried at 40° C. under vacuum. The compound 1-(3′,4′-dichloro-2-fluoro[1,1′-biphenyl]-4-yl)-cyclopropanecarboxylic acid is obtained as a white powder (10.3 g, 68% yield).

Workup

  1. additionis added portionwise
  2. temperaturethe mixture is refluxed for 48 hours
  3. temperatureThe reaction mixture is cooled
  4. filtrationfiltered
  5. washthe solid is repeatedly washed with water
  6. customdried at 40° C. under vacuum
  7. dissolutionThe crude product is dissolved
  8. temperaturein refluxing 2-propanol (178 ml)
  9. additionthe solution is mixed with activated carbon (0.3 g)
  10. stirringstirred
  11. temperatureat reflux
  12. filtrationfiltered
  13. concentrationconcentrated
  14. additionmixed with n-heptane (116 ml)
  15. filtrationthe crystallized solid is filtered
  16. washwashed with 2-propanol
  17. customdried at 40° C. under vacuum

Sources & evidence

ORD record
ord-46ac11ed8897497dbca457f794200b6d
Source dataset
uspto-grants-2015_06
Patent number
US09056818B2

Reaction notes

Loading…