Potassium Phosphate, Tribasic → Methyl 2-(4-methylphenyl)-6-(prop-1-en-2-yl)pyridine-4-carboxylate

HRID 1909127Notes

Reaction equation

HRID 1909127 reaction equation
CO[C:3]1[CH:8]=CC=C[C:4]=1P(C1C=CC=CC=1OC)C1C=CC=CC=1OC.Cl[C:27]1[CH:28]=[C:29]([CH:34]=[C:35](Cl)[N:36]=1)[C:30]([O:32][CH3:33])=[O:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(B1OC(C)(C)C(C)(C)O1)(C)=C.[CH3:58][C:59]1[CH:64]=[CH:63][C:62](B(O)O)=[CH:61][CH:60]=1.C([O-])(O)=O.[Na+]>C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:58][C:59]1[CH:64]=[CH:63][C:62]([C:27]2[CH:28]=[C:29]([C:30]([O:32][CH3:33])=[O:31])[CH:34]=[C:35]([C:3]([CH3:8])=[CH2:4])[N:36]=2)=[CH:61][CH:60]=1

Participants

10

Reactant 6

HCID 62657Potassium Phosphate, TribasicHCID 78464Tris(o-methoxyphenyl)phosphine2×HCID 79799Tolylboronic acid2×HCID 93237Methyl 2,6-dichloroisonicotinateHCID 516892Sodium BicarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane

Product 1

HCID 67339741Methyl 2-(4-methylphenyl)-6-(prop-1-en-2-yl)pyridine-4-carboxylateYield 376%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
63 °C

Procedure

To a degassed solution of palladium(II) acetate (21.8 mg, 0.10 mmol) and tris(2-methoxyphenyl)phosphine (68.4 mg, 0.19 mmol) in THF (1 mL) was added a degassed mixture of methyl 2,6-dichloroisonicotinate (250 mg, 1.21 mmol), tripotassium phosphate (386 mg, 1.82 mmol), and 2-isopropenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.285 mL, 1.52 mmol) in THF (1.5 mL) and water (0.625 mL). The mixture was heated to 63° C. After 4 h, a degassed solution of 4-methylphenylboronic acid (247 mg, 1.82 mmol) in THF (1.25 mL) was added. The resulting mixture was heated to 63° C. After 18 h, 4-methylphenylboronic acid (247 mg, 1.82 mmol), palladium(II) acetate (21.8 mg, 0.10 mmol), and tris(2-methoxyphenyl)phosphine (68.4 mg, 0.19 mmol) were added. The resulting mixture was heated to 63° C. After 18 h, the mixture was cooled to ambient temperature. Saturated aqueous NaHCO3 was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase chromatography (C-18, 80% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (191 mg). MS 268.1 (M+1).

Workup

  1. temperatureThe resulting mixture was heated to 63° C
  2. waitAfter 18 h
  3. temperatureThe resulting mixture was heated to 63° C
  4. waitAfter 18 h
  5. temperaturethe mixture was cooled to ambient temperature
  6. extractionthe mixture was extracted with ethyl acetate (3×)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by reverse phase chromatography (C-18, 80% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-4d2289fec9124af6a0c73a286e978a5c
Source dataset
uspto-grants-2013_12
Patent number
US08598209B2

Reaction notes

Loading…