Potassium Phosphate, Tribasic → 1-(4-hydroxy-3-methoxyphenyl)-4-(4-(trifluoromethoxy)phenyl)pyridin-2(1H)-one

HRID 1044414Notes

Reaction equation

HRID 1044414 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14]COCC[Si](C)(C)C)=[C:10]([O:23][CH3:24])[CH:9]=2)[C:4](=[O:25])[CH:3]=1.[F:26][C:27]([F:39])([F:38])[O:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:14][C:11]1[CH:12]=[CH:13][C:8]([N:5]2[CH:6]=[CH:7][C:2]([C:29]3[CH:30]=[CH:31][C:32]([C:27]([F:39])([F:38])[F:26])=[CH:33][CH:34]=3)=[CH:3][C:4]2=[O:25])=[CH:9][C:10]=1[O:23][CH3:24].[OH:14][C:11]1[CH:12]=[CH:13][C:8]([N:5]2[CH:6]=[CH:7][C:2]([C:32]3[CH:31]=[CH:30][C:29]([O:28][C:27]([F:26])([F:38])[F:39])=[CH:34][CH:33]=3)=[CH:3][C:4]2=[O:25])=[CH:9][C:10]=1[O:23][CH3:24]

Participants

8

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 585802544-chloro-1-(3-methoxy-4-((2-(trimethylsilyl)ethoxy)methoxy)phenyl)pyridin-2(1H)-one

Product 2

HCID 671348191-(4-hydroxy-3-methoxyphenyl)-4-(4-(trifluoromethoxy)phenyl)pyridin-2(1H)-oneYield 85%HCID 671350841-(4-hydroxy-3-methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-chloro-1-(3-methoxy-4-((2-(trimethylsilyl)ethoxy)methoxy)phenyl)-pyridin-2(1H)-one Part A (118 mg, 0.31 mmol), 4-(trifluoromethoxy)phenylboronic acid (95 mg, 0.463 mmol), Potassium phosphate tribasic (197 mg, 0.93 mmol), and PalladiumTetrakis (18 mg, 0.02 mmol) in DMF (1.5 mL) was stirred under nitrogen at 90° C. overnight. The mixture was diluted with DCM, filtered, and concentrated. The crude was dissolved in 10:90 MeOH/CH2Cl2 (5 mL) and 4N HCl in dioxane (1 mL) was added. The mixture was stirred for 30 min at RT. Concentrated and the residue was purified using ISCO flash chromatography (silica gel/hexanes/ethyl acetate/methanol 100:0 to 0:90:10 gradient) to afford the desired product 1-(4-hydroxy-3-methoxyphenyl)-4-(4-(trifluoromethoxy)phenyl)pyridin-2(1H)-one 14B (99 mg, 0.26 mmol, 85% yield) as a yellow solid. LC/MS 362 (M+H)+, tR 0.89 min (method 5).

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. dissolutionThe crude was dissolved in 10:90 MeOH/CH2Cl2 (5 mL) and 4N HCl in dioxane (1 mL)
  4. additionwas added
  5. stirringThe mixture was stirred for 30 min at RT
  6. concentrationConcentrated
  7. customthe residue was purified

Sources & evidence

ORD record
ord-07e6776d0bf349d3983fb4deb62276c2
Source dataset
uspto-grants-2013_10
Patent number
US08563583B2

Reaction notes

Loading…