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

HRID 717814Notes

Reaction equation

HRID 717814 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 83%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A solution of methyl 2,5-dichloronicotinate (8.2 g, 40 mmol), (3-fluorophenyl)boronic acid (6.1 g, 44 mmol), and potassium carbonate (12 g, 86 mmol) in water (71 mL) and 1,4-dioxane (190 mL) was degassed with nitrogen (10 minutes). The reaction mixture was treated with bis(triphenylphosphine)palladium(II) chloride (3.1 g, 4.4 mmol), degassed with nitrogen (10 minutes), and heated at 80° C. for 14.5 hours. The reaction mixture was diluted with ethyl acetate and water and filtered over celite. The aqueous layer was separated and re-extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried with magnesium sulfate, filtered, and concentrated to a crude residue. Purification by flash column chromatography using ethyl acetate in hexanes (0-80%) gave the desired product (8.7 g, 83%). LCMS calculated for C13H10ClFNO2 (M+H)+: m/z=266.0. found: 265.8.

Workup

  1. customdegassed with nitrogen (10 minutes)
  2. additionThe reaction mixture was diluted with ethyl acetate and water
  3. filtrationfiltered over celite
  4. customThe aqueous layer was separated
  5. extractionre-extracted with ethyl acetate
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialdried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a crude residue
  10. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-26d8ebe933b34a42bcd68ba333d6a270
Source dataset
uspto-grants-2015_11
Patent number
US09193721B2

Reaction notes

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