Potassium Phosphate, Tribasic → Methyl 2-(2,4-difluorophenyl)-6-isopropenylisonicotinate

HRID 1909124Notes

Reaction equation

HRID 1909124 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[C:10](Cl)[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].P([O-])([O-])([O-])=O.[K+].[K+].[K+].CO[C:23]1[CH:28]=CC=C[C:24]=1P(C1C=CC=CC=1OC)C1C=CC=CC=1OC.C(B1OC(C)(C)C(C)(C)O1)(C)=C.[F:58][C:59]1[CH:64]=[C:63]([F:65])[CH:62]=[CH:61][C:60]=1B(O)O.C([O-])(O)=O.[Na+]>C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:58][C:59]1[CH:64]=[C:63]([F:65])[CH:62]=[CH:61][C:60]=1[C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:23]([CH3:28])=[CH2:24])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

10

Reactant 6

HCID 62657Potassium Phosphate, TribasicHCID 78464Tris(o-methoxyphenyl)phosphineHCID 93237Methyl 2,6-dichloroisonicotinateHCID 516892Sodium BicarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane

Product 1

HCID 67339607Methyl 2-(2,4-difluorophenyl)-6-isopropenylisonicotinateYield 622.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

To a degassed solution of methyl 2,6-dichloroisonicotinate (0.1 g, 0.49 mmol), tripotassium phosphate (0.16 g, 0.73 mmol), palladium(II) acetate (8.72 mg, 0.04 mmol) and tris(2-methoxyphenyl)phosphine (27.4 mg, 0.08 mmol) in THF (1 mL) and water (0.25 mL) was added 2-isopropenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.11 mL, 0.61 mmol)) The mixture was heated to 65° C. After 4 h, a solution of (2,4-difluorophenyl)boronic acid (0.12 g, 0.73 mmol) in THF (0.5 mL) was added. The mixture was continued to stir at 65° C. After 18 h, the mixture was cooled to ambient temperature. Saturated aqueous NaHCO3 was added 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 silica gel chromatography (100% hexanes→90% hexanes/ethyl acetate) gave the title compound (144 mg, 80% pure). MS 290.1 (M+1).

Workup

  1. waitAfter 18 h
  2. temperaturethe mixture was cooled to ambient temperature
  3. extractionwas extracted with ethyl acetate (3×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (100% hexanes→90% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-90e047dd41304f0c9670671b3b121b53
Source dataset
uspto-grants-2013_12
Patent number
US08598209B2

Reaction notes

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