Hydrochloric Acid → 2-Hydroxy-4-[(5-nitro-2-pyridinyl)oxy]benzonitrile

HRID 527730

Reaction equation

[OH:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Cl[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][N:13]=1.C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.CCOCC.O>[OH:1][C:2]1[CH:9]=[C:8]([O:10][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][N:13]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

Conditions

Temperature: 110 °C

Procedure

In a vial 2,4-dihydroxybenzonitrile (300 mg, 2.2 mmol), 2-chloro-5-nitropyridine (351.96 mg, 2.22 mmol) and K2CO3 (920 mg, 6.62 mmol) were dissolved in DMF (5 mL). The reaction was heated for 1 hour under microwave irradiations (Set Temperature: 110° C.). The reaction mixture was diluted with Et2O and water, acidified with aqueous 1N HCl until pH=2, the phases were separated and the organics were dried over Na2SO4. The solid was filtered out and the solvent was removed affording crude 2-hydroxy-4-[(5-nitro-2-pyridinyl)oxy]benzonitrile (664 mg) as a brown solid. To a solution of this crude in dry DMF (5 mL) potassium carbonate (460 mg, 3.33 mmol) and isopropyl bromide (313 μL, 3.33 mmol) were added and the reaction mixture was stirred overnight at 50° C. The reaction was diluted with brine (10 mL) and extracted with ethyl acetate (2×20 mL). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography on silica gel (SNAP 25 g) eluting from 100:0 to 75:25 cyclohexane/ethyl acetate affording the title compound (260 mg) as white solid.

Workup

customthe phases were separated
dry with materialthe organics were dried over Na2SO4
filtrationThe solid was filtered out
customthe solvent was removed

Sources & evidence

ORD record: ord-41fbe47ed6b24a01b98753c35d016beb
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346790B2

Linked notes

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