1,4-Dioxane → 2-Fluoro-3-(2-methoxy-4-nitrophenyl)pyridine

HRID 218520Notes

Reaction equation

HRID 218520 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH3:12].[F:13][C:14]1[C:19](B(O)O)=[CH:18][CH:17]=[CH:16][N:15]=1.C(=O)([O-])O.[Na+].O1CCOCC1>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:13][C:14]1[C:19]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=2[O:11][CH3:12])=[CH:18][CH:17]=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 2301031-Iodo-2-methoxy-4-nitrobenzeneHCID 516892Sodium BicarbonateHCID 27832702-Fluoropyridine-3-boronic acid

Product 1

HCID 595867372-Fluoro-3-(2-methoxy-4-nitrophenyl)pyridine

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×

Procedure

2.00 g (7.17 mmol) of 2-iodo-5-nitroanisole, 2.02 g (14.3 mmol) of (2-fluoropyridin-3-yl)boronic acid (A. Bouillon, J.-C. Lancelot, V. Collot, P. R. Bovy, S. Rault, Tetrahedron 2002, 58, 3323-3328.), 1.81 g (21.5 mmol) of sodium hydrogen carbonate and 117 mg (0.14 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]palladium dichloride are heated to 100° C. in a degassed mixture of 40 ml of dioxane and 10 ml of water for 1 h. After cooling, the mixture is diluted with water and extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulfate, clarified over activated carbon and concentrated. Purification is effected by chromatography on silica gel (eluent: dichloromethane) to obtain 1.55 g (87% of theory) of the desired product.

Workup

  1. temperatureAfter cooling
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic phases are dried over sodium sulfate
  4. concentrationconcentrated
  5. customPurification

Sources & evidence

ORD record
ord-ff579b8070394bb5872f49f6b21404b3
Source dataset
uspto-grants-2012_06
Patent number
US08198267B2

Reaction notes

Loading…