Phenol → 8-Bromo-3-methyl-2-phenoxyquinoline

HRID 1055926Notes

Reaction equation

[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18](Cl)[C:17]([CH3:22])=[CH:16]2>CN(C=O)C>[Br:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[N:19]=[C:18]([O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:17]([CH3:22])=[CH:16]2

Participants

Conditions

Temperature: 25 °C

Procedure

Phenol (954 mg, 10.14 mmol) was added to a suspension of NaH (60% w/w in mineral oil; 406 mg, 10.14 mmol) in DMF (10 mL) at 0° C. and the resulting solution was stirred at 25° C. for 15 min. 8-Bromo-2-chloro-3-methylquinoline (510 mg, 1.988 mmol) was then added, and the resulting solution was heated at 60° C. for 2.5 d. The mixture was cooled to 25° C. and partitioned between EtOAc (100 mL) and saturated aq. NH4Cl (80 mL). The organic layer was separated, sequentially washed with water (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% EtOAc/hexanes) furnished 8-bromo-3-methyl-2-phenoxyquinoline (505.5 mg, 1.609 mmol, 81% yield) as a colorless oil, which was used without further purification in the subsequent step: m/z (ESI, +ve) 314.0 (M+H)+.

Workup

temperaturethe resulting solution was heated at 60° C. for 2.5 d
temperatureThe mixture was cooled to 25° C.
custompartitioned between EtOAc (100 mL) and saturated aq. NH4Cl (80 mL)
customThe organic layer was separated
washsequentially washed with water (2×50 mL) and brine (50 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customChromatographic purification of the residue (silica gel, 0-10% EtOAc/hexanes)

Sources & evidence

ORD record: ord-85ce49f1704d42c9be1e5e03e37e1831
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

Loading…