Sodium Carbonate → 2-Fluoro-3-(2-methylpyridin-4-yl)pyridine

HRID 1846752Notes

Reaction equation

HRID 1846752 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.[F:9][C:10]1[C:15](B(O)O)=[CH:14][CH:13]=[CH:12][N:11]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(O)C.O.C(=O)(O)[O-].[Na+].O.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>[F:9][C:10]1[C:15]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=2)=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27628354-Bromo-2-methylpyridineHCID 27832702-Fluoropyridine-3-boronic acid

Product 1

HCID 585485722-Fluoro-3-(2-methylpyridin-4-yl)pyridineYield 81.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 516892Sodium BicarbonateSolventHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-bromo-2-methylpyridine (25.0 g, 145 mmol), 2-fluoropyridin-3-ylboronic acid (22.5 g, 160 mmol), Pd(PPh3)2Cl2 (5.10 g, 7.27 mmol), and sodium carbonate (46.2 g, 436 mmol) in 1,2-dimethoxyethane:ethanol:water (7:2:0.75, 292.5 ml total volume) was heated to 80° C. for 4 h. After cooling to room temperature, the mixture was diluted with saturated aqueous sodium bicarbonate solution and water, then extracted with dichloromethane (3×). The combined organic extracts were then extracted with 2 N aqueous HCl solution (4×). The combined aqueous layers were washed with dichloromethane, then the pH was raised to 10 with 10 N NaOH. The resulting suspension was extracted with dichloromethane (3×). The combined extracts were concentrated in vacuo to give 2-fluoro-3-(2-methylpyridin-4-yl)pyridine (22.14 g, 118 mmol, 81% yield).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with dichloromethane (3×)
  3. extractionThe combined organic extracts were then extracted with 2 N aqueous HCl solution (4×)
  4. washThe combined aqueous layers were washed with dichloromethane
  5. temperaturethe pH was raised to 10 with 10 N NaOH
  6. extractionThe resulting suspension was extracted with dichloromethane (3×)
  7. concentrationThe combined extracts were concentrated in vacuo

Sources & evidence

ORD record
ord-01afd3a5e9af4b3fb984c3e228286d48
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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