Hydrochloric Acid → 3-(2,6-Dichloro-4-nitro-phenoxy)-6-methyl-quinoline

HRID 1819766Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH3:12])=[CH:7][CH:6]=2.[H-].[Na+].[Cl:15][C:16]1[CH:17]=[C:18]([N+:24]([O-:26])=[O:25])[CH:19]=[C:20]([Cl:23])[C:21]=1Cl.Cl>CN(C=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([N+:24]([O-:26])=[O:25])[CH:19]=[C:20]([Cl:23])[C:21]=1[O:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH3:12])=[CH:7][CH:6]=2

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 3-Hydroxy-6-methylquinoline (92) (348 mg, 2.19 mmol) in DMF (3.5 mL), was added NaH (60% oil suspension, 90 mg, 2.25 mmol) in one portion at room temperature. After 5 min 3,4,5-trichloronitrobenzene (509 mg, 2.25 mmol) in DMF (2 mL) was added and the reaction mixture was heated at 50° C. with stirring for 2 h. After cooling to room temperature. Ice/water was added to the reaction mixture, which was then acidified with 2N HCl and extracted twice with AcOEt. Organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated. Crude residue was purified by column chromatography (hexane/AcOEt4/1, 80 g of silica gel) to afford compound 93 (510 mg, 67%). 1H NMR (300 MHz, DMSO-d6) δ 7.52-7.57 (2H, m), 7.61 (1H, s), 7.94 (1H, d, J=8.6 Hz), 8.63 (2H, s), 8.86 (1H, d, J=2.9 Hz).

Workup

temperatureAfter cooling to room temperature
extractionextracted twice with AcOEt
washOrganic layer was washed with brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated
customCrude residue was purified by column chromatography (hexane/AcOEt4/1, 80 g of silica gel)

Sources & evidence

ORD record: ord-df407a6db1da48d3b2ad1c805493b538
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07601841B2

Reaction notes

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