Methyl iodide → 3-acetyl-8-bromo-1-methylquinolin-4(1H)-one

HRID 525878Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 3-acetyl-8-bromoquinolin-4(1H)-one (5.35 g, 20.11 mmol) and K2CO3 (9.17 g, 66.3 mmol) in dry N,N-dimethylformamide (100 mL) was heated at 90° C. for 30 min. After cooling to room temperature, iodomethane (3.77 mL, 60.3 mmol) was added and the mixture was stirred again at 90° C. for 2 h. Then the reaction mixture was concentrated and diluted with water (50 mL), extracted with dichloromethane (4×50 mL), dried over sodium sulfate and absorbed onto silica gel. Purification by automatic silica gel column chromatography (Combiflash RF) eluting with ethyl acetate/hexanes (10-100%) afforded 3-acetyl-8-bromo-1-methylquinolin-4(1H)-one (3.4 g, 12.14 mmol, 60.4% yield) as a brown solid. LCMS: (M+H)+: 279.9.

Workup

temperatureAfter cooling to room temperature
concentrationThen the reaction mixture was concentrated
additiondiluted with water (50 mL)
extractionextracted with dichloromethane (4×50 mL)
dry with materialdried over sodium sulfate
customabsorbed onto silica gel
customPurification by automatic silica gel column chromatography (Combiflash RF)
washeluting with ethyl acetate/hexanes (10-100%)

Sources & evidence

ORD record: ord-b116b73f57434d1a938a1ccc8d594761
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340556B2

Reaction notes

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