Potassium Carbonate → 4-Chloro-6,7-dimethoxy-quinoline-3-carbonitrile

HRID 132543Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[NH:9][CH:8]=[C:7]([C:15]#[N:16])[C:6]2=O.O=P(Cl)(Cl)[Cl:20].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[Cl:20][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][C:7]=1[C:15]#[N:16]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile (from Step B, 20 g, 87 mmol) and POCl3 (87 mL) was heated to reflux and allowed to stir for 2 hours. The reaction mixture was cooled to 70° C. and concentrated in vacuo to provide a crude residue. The crude residue was diluted with methylene chloride and the resultant solution was cooled to 0° C. and to the resultant solution was added aqueous K2CO3 until the solution was at pH 8-9. The resultant solution was allowed to stir for 30 minutes at 25° C., then transferred to a separatory funnel. The organic layer was collected, washed with water, dried over sodium sulfate, filtered through celite, and concentrated in vacuo to provide 4-chloro-6,7-dimethoxyquinoline-3-carbonitrile as an off-white solid (19.8 g, 92%). A sample recrystallized from methylene chloride was characterized as follows: mp 220-223° C.; 1H NMR (DMSO-d6)δ 8.98 (s, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 4.02 (s, 3H), 4.01 (s, 3H).

Workup

temperaturewas heated
temperatureto reflux
concentrationconcentrated in vacuo
customto provide a crude residue
stirringto stir for 30 minutes at 25° C.
customtransferred to a separatory funnel
customThe organic layer was collected
washwashed with water
dry with materialdried over sodium sulfate
filtrationfiltered through celite
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-99871cf91aef4aea9819aa3289ef2ad6
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07388016B2

Reaction notes

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