Water → Methyl 5-(benzyloxy)-6-(2-fluoro-5-methoxyphenyl)nicotinate

HRID 709796Notes

Reaction equation

[CH2:1]([O:8][C:9]1[C:10](Cl)=[N:11][CH:12]=[C:13]([CH:18]=1)[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[CH2:1]([O:8][C:9]1[C:10]([C:22]2[CH:23]=[C:24]([O:27][CH3:28])[CH:25]=[CH:26][C:21]=2[F:20])=[N:11][CH:12]=[C:13]([CH:18]=1)[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Under a nitrogen atmosphere, to a solution of methyl 5-(benzyloxy)-6chloronicotinate (2.77 g) in 1,4-dioxane (100 mL) were added 2-fluoro-5methoxyphenylboronic acid (2.00 g), potassium carbonate (2.76 g), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (36 mg) and water (10 mL), and the mixture was stirred at 80° C. for 20 hr. The reaction mixture was concentrated, and the residue was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the title compound (3.50 g) as a colorless oil.

Workup

concentrationThe reaction mixture was concentrated
extractionthe residue was extracted with ethyl acetate
washThe extract was washed with saturated brine
dry with materialdried over anhydrous sodium sulfate
customThe solvent was evaporated under reduced pressure
customthe residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate)

Sources & evidence

ORD record: ord-8f1257b230414b179698f89fa52ea2b6
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181186B2

Reaction notes

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