Potassium Carbonate → 2-Methylpyridine-3-carbonitrile

HRID 7153

Reaction equation

HRID 7153 reaction equation
[C:1]([C:3]1[C:4](Cl)=[N:5][CH:6]=[CH:7][CH:8]=1)#[N:2].[CH3:10]B(O)O.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[C:4]([CH3:10])=[N:5][CH:6]=[CH:7][CH:8]=1)#[N:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 810792-ChloronicotinonitrileHCID 139377Methylboronic Acid

Product 1

HCID 47383082-Methylpyridine-3-carbonitrileYield 46.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 3-cyano-2-chloro-pyridine (422 mg, 3.05 mmol), methylboronic acid (209 mg, 3.49 mmol) and K2CO3 (1.22 g, 8.83 mmol) in degassed dioxane (5 mL) under argon was added Pd(PPh3)4 (222 mg, 0.19 mmol) and the mixture stirred at reflux over the weekend. The reaction was cooled to room temperature, diluted with CH2Cl2 (20 mL) and filtered through Celite, washing the cake with CH2Cl2 and MeOH. The filtrate was concentrated in vacuo and purified by column chromatography on silica gel (Hexanes/ethyl acetate, 9:1 then 4:1) to afford the desired product (166 mg, 46%) as a white solid. 1H NMR (CDCl3): δ 2.78 (s, 3H), 7.25 (dd, 1H, J=9, 6 Hz), 7.90 (dd, 1H, J=6, 3 Hz), 8.69 (d, 1H, J=3 Hz).

Workup

  1. temperatureat reflux over the weekend
  2. filtrationfiltered through Celite
  3. washwashing the cake with CH2Cl2 and MeOH
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified by column chromatography on silica gel (Hexanes/ethyl acetate, 9:1

Sources & evidence

ORD record
ord-993a754e79ee4cedb82df3462a06dec6
Source dataset
uspto-grants-2006_08
Patent number
US07084155B2

Linked notes

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