Hydrochloric Acid → 4-(5-Chloro-2-hydroxyphenyl)pyridine-2-carbonitrile

HRID 46330

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6](B(O)O)[CH:7]=1.Cl[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([C:19]#[N:20])[CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>O1CCOCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([C:19]#[N:20])[CH:14]=2)[CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

(5-Chloro-2-hydroxyphenyl)boronic acid (2.0 g, 0.012 mol), 4-chloropyridine-2-carbonitrile (1.61 g, 0.012 mol), (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (0.424 g, 0.00058 mol) and sodium carbonate (3.7 g, 0.035 mol) in 1,4-dioxane (20.0 mL) and deionised water (1.0 mL) were degassed with nitrogen (×3) before heating at 100° C. for 18 hours under nitrogen. The reaction was cooled and hydrochloric acid (2.0 M aqueous solution, 30.0 mL) added. Reaction was filtered, washing with ethyl acetate (50.0 mL). The organic layer was concentrated in vacuo and purified by flash column chromatography on the ISCO™ (40 g SiO2) eluting with ethyl acetate:heptane (gradient 0:1 to 7:3, by volume) to afford the title compound as a yellow solid, 0.23 g, 8.6% yield.

Workup

temperatureThe reaction was cooled
customReaction
filtrationwas filtered
washwashing with ethyl acetate (50.0 mL)
concentrationThe organic layer was concentrated in vacuo
custompurified by flash column chromatography on the ISCO™ (40 g SiO2)
washeluting with ethyl acetate

Sources & evidence

ORD record: ord-6274da3e6fdd4badbbf2fa3c0e80ad14
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541588B2

Linked notes

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