Dichloromethane → HCID 57411214, compound

HRID 623885Notes

Reaction equation

HRID 623885 reaction equation
C(Cl)Cl.C(O)(=O)C.[C:8]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:18]([CH3:32])=[CH:19][C:20]([O:23][CH2:24][C:25]([CH3:31])([CH3:30])[C:26]([O:28]C)=[O:27])=[N:21][CH:22]=2)=[CH:13][C:12]=1[F:33])(=[NH:10])[NH2:9].Br[CH2:35][C:36]([C:38]1([C:41]([F:44])([F:43])[F:42])[CH2:40][CH2:39]1)=O.C(=O)([O-])[O-].[K+].[K+]>[Cl-].[Na+].O>[F:33][C:12]1[CH:13]=[C:14]([C:17]2[C:18]([CH3:32])=[CH:19][C:20]([O:23][CH2:24][C:25]([CH3:30])([CH3:31])[C:26]([OH:28])=[O:27])=[N:21][CH:22]=2)[CH:15]=[CH:16][C:11]=1[C:8]1[NH:10][C:36]([C:38]2([C:41]([F:44])([F:43])[F:42])[CH2:40][CH2:39]2)=[CH:35][N:9]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 67973349HCID 67973349, compoundHCID 866981711382999-80-5

Product 1

HCID 57411214HCID 57411214, compoundYield 74.5%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

A mixture in which methylene chloride (8 mL) and a saturated brine (8 mL) were added to methyl 3-{[5-(4-carbamimidoyl-3-fluorophenyl)-4-methylpyridin-2-yl]oxy}-2,2-dimethylpropanoate acetic acid salt (400 mg), 2-bromo-1-[1-(trifluoromethyl)-cyclopropyl]ethanone (289 mg) and potassium carbonate (404 mg) was stirred at 50° C. for 8 hours. The organic layer was separated, and concentrated under reduced pressure. The obtained residue was dissolved in tetrahydrofuran (2.0 mL) and methanol (2.0 mL), and after adding 2N aqueous sodium hydroxide solution (3.0 mL) to the solution, the resulting mixture was stirred at 50° C. for 3 hours. The mixture was diluted by ethyl acetate, and then, neutralized by adding 1N hydrochloric acid. The organic layer was separated, ether was added to the residue obtained by concentrating the mixture under reduced pressure and the resulting mixture was stirred. The precipitated solid was collected by filtration and dried to obtain 3-{[5-(3-fluoro-4-{5-[1-(trifluoromethyl)cyclopropyl]-1H-imidazol-2-yl]phenyl)-4-methylpyridin-2-yl}oxy}-2,2-dimethylpropanoic acid (339 mg).

Workup

  1. customThe organic layer was separated
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe obtained residue was dissolved in tetrahydrofuran (2.0 mL)
  4. additionmethanol (2.0 mL), and after adding 2N aqueous sodium hydroxide solution (3.0 mL) to the solution
  5. stirringthe resulting mixture was stirred at 50° C. for 3 hours
  6. additionThe mixture was diluted by ethyl acetate
  7. additionby adding 1N hydrochloric acid
  8. customThe organic layer was separated
  9. additionether was added to the residue
  10. customobtained
  11. concentrationby concentrating the mixture under reduced pressure
  12. stirringthe resulting mixture was stirred
  13. filtrationThe precipitated solid was collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-651c47c9eae8461c87b7b6b738bf6b8d
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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