Potassium Carbonate → Methyl 5-chloro-2-(3-fluorophenyl)nicotinate

HRID 717852Notes

Reaction equation

HRID 717852 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>O.O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:12][C:9]1[CH:10]=[N:11][C:2]([C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([F:13])[CH:19]=2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 2764318Methyl 2,5-Dichloronicotinate

Product 1

HCID 58515983Methyl 5-chloro-2-(3-fluorophenyl)nicotinateYield 79%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of methyl 2,5-dichloronicotinate (27.0 g, 131 mmol), (3-fluorophenyl)boronic acid (20.2 g, 144 mmol), and potassium carbonate (39.5 g, 286 mmol) in water (190 mL) and 1,4-dioxane (578 mL) was degassed with nitrogen (10 min). The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (5.2 g, 7.4 mmol), degassed with nitrogen (10 min), and heated at 80° C. for 18 hours. The reaction was complete, allowed to cool to room temperature and partitioned between ethyl acetate and water. The combined organic layer was washed with water, brine, dried over magnesium sulfate, filtered, and concentrated to give the crude residue product as a dark oil. The product was purified on silica gel eluting with hexane:ethyl acetate gradient to give methyl 5-chloro-2-(3-fluorophenyl)nicotinate (27.5 g, 79%) as a white solid. LCMS calculated for C13H10ClFNO2(M+H)+: m/z=266.0. found: 265.9.

Workup

  1. customdegassed with nitrogen (10 min)
  2. temperatureto cool to room temperature
  3. custompartitioned between ethyl acetate and water
  4. washThe combined organic layer was washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude residue product as a dark oil
  9. customThe product was purified on silica gel eluting with hexane

Sources & evidence

ORD record
ord-fe951d77943d4fc1af309903b2315177
Source dataset
uspto-grants-2015_11
Patent number
US09193721B2

Reaction notes

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