Potassium Carbonate → Isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetate

HRID 1771603Notes

Reaction equation

HRID 1771603 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11]2[C:12]([F:26])=[C:13]([CH:22]=[CH:23][C:24]=2[F:25])[O:14][CH2:15][C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[F:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C([O-])([O-])=O.[K+].[K+]>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:26][C:12]1[C:11]([NH:10][CH2:9][C:4]2[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([F:27])[CH:33]=3)[CH:3]=2)=[C:24]([F:25])[CH:23]=[CH:22][C:13]=1[O:14][CH2:15][C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 89444123Isopropyl 2-[3-[(3-bromo-5-methyl-phenyl)methylamino]-2,4-difluoro-phenoxy]acetate

Product 1

HCID 89443771Isopropyl 2-[2,4-difluoro-3-[[3-(3-fluorophenyl)-5-methyl-phenyl]methylamino]phenoxy]acetateYield 78.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of isopropyl 2-[3-[(3-bromo-5-methyl-phenyl)methylamino]-2,4-difluoro-phenoxy]acetate (176 mg, 0.4 mmol, 1.0 eq) in acetonitrile (15 mL) was added 3-fluorophenylboronic acid (86 mg, 0.61 mmol, 1.5 eq), K2CO3 (142 mg, 1.03 mmol, 2.5 eq) and Pd(dppf)Cl2 (15 mg, 0.02 mmol, 0.05 eq). The mixture was heated at reflux overnight then the solvent was removed in vacuo. The residue was diluted with CH2Cl2, washed with water, dried (MgSO4), filtered and evaporated in vacuo. The residue was purified by chromatography (petroleum ether: EtOAc, 150:1 to 60:1) to give the title compound as an oil (140 mg, 77%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux overnight
  3. customthe solvent was removed in vacuo
  4. additionThe residue was diluted with CH2Cl2
  5. washwashed with water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by chromatography (petroleum ether: EtOAc, 150:1 to 60:1)

Sources & evidence

ORD record
ord-2afb127fd68d4453a93ce275a8597b16
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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