1,4-Dioxane → Methyl 4-(2-fluoro-5-methylpyridin-4-yl)benzoate

HRID 968686

Reaction equation

[F:1][C:2]1[CH:7]=[C:6](I)[C:5]([CH3:9])=[CH:4][N:3]=1.C([CH2:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1)(O)=O.P([O-])([O-])([O-])=[O:24].[K+].[K+].[K+].[O:31]1CCOC[CH2:32]1>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[CH3:32][O:31][C:13](=[O:24])[C:14]1[CH:15]=[CH:16][C:17]([C:6]2[C:5]([CH3:9])=[CH:4][N:3]=[C:2]([F:1])[CH:7]=2)=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 95 °C

Procedure

2-Fluoro-4-iodo-5-methyl-pyridine (0.90 g, 3.8 mmol), 4-carboxymethyl-phenyl boronic acid (0.72 g, 4.0 mmol), potassium phosphate (2.5 g, 11.8 mmol), and dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium (II) dichloromethane adduct (0.30 g, 0.37 mmol) were combined in a screw cap tube and 1.4-dioxane (20 mL) was added. Argon was bubbled through the reaction mixture, which was then sealed and heated to 95° C. overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to a red solid, which was purified by chromatography on silica (EtOAc 0 to 40% in hexanes) to afford 4-(2-fluoro-5-methyl-pyridin-4-yl)-benzoic acid methyl ester, 0.62 g, 2.5 mmol, 66% yield. 1H NMR 500 MHz (CDCl3): 8.05 (m, 3H), 7.33 (d, 2H), 6.74 (s, 1H), 3.90 (s, 3H), 2.15 (s, 3H).

Workup

customcap tube
customArgon was bubbled through the reaction mixture, which
customwas then sealed
additionThe reaction mixture was diluted with water
extractionextracted with ethyl acetate
dry with materialThe organic layer was dried over sodium sulfate
concentrationconcentrated to a red solid, which
customwas purified by chromatography on silica (EtOAc 0 to 40% in hexanes)

Sources & evidence

ORD record: ord-b0a490c0fb064421941dd2662e58f206
Source dataset: uspto-grants-2007_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07304071B2

Linked notes

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