Ethyl Acetate → Methyl 4-hydroxy-3'-methyl-5'-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-carboxylate

HRID 530409Notes

Reaction equation

HRID 530409 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:9](I)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(=O)([O-])[O-].[Na+].[Na+].[CH3:19][C:20]1[CH:21]=[C:22]([NH:35][C:36]2[N:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][N:37]=2)[CH:23]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:25]=1.C(OCC)(=O)C>O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[OH:1][C:2]1[CH:11]=[CH:10][C:9]([C:24]2[CH:23]=[C:22]([NH:35][C:36]3[N:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[CH:38][N:37]=3)[CH:21]=[C:20]([CH3:19])[CH:25]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 248910Methyl 5-IodosalicylateHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 90041756Methyl 4-hydroxy-3'-methyl-5'-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-carboxylate

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 2-hydroxy-5-iodobenzoate (11.6 g, 41.5 mmol) in 2-methyl-THF (180 mL) and water (82.5 mL) was purged with N2 for 30 minutes. Sodium carbonate (12.6 g, 119 mmol), N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (15.0 g, 39.6 mmol) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.61 g, 1.98 mmol) were added to the reaction mixture at rt under N2 and then the mixture was heated to 80° C. for 14 hours. The reaction mixture was poured into a 1:1 solution of ethyl acetate/2N HCl (800 mL) and the layers were separated. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) to afford methyl 4-hydroxy-3′-methyl-5′-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-carboxylate. MS ESI calcd. for C20H12F3N3O3 [M+H]+ 404, found 404.

Workup

  1. customwas purged with N2 for 30 minutes
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a68f91da7b164762ab11fcc32388105c
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

Loading…