5-((4-Bromo-5-fluoro-2-methoxyphenoxy)methyl)-2-methoxypyridine → 2-Fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzonitrile

HRID 2178343Notes

Reaction equation

Br[C:2]1[C:17]([F:18])=[CH:16][C:5]([O:6][CH2:7][C:8]2[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[N:12][CH:13]=2)=[C:4]([O:19][CH3:20])[CH:3]=1.[Cu][C:22]#[N:23]>CN(C)C=O.ClCCl>[F:18][C:17]1[CH:16]=[C:5]([O:6][CH2:7][C:8]2[CH:13]=[N:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[C:4]([O:19][CH3:20])=[CH:3][C:2]=1[C:22]#[N:23]

Participants

Conditions

Temperature: 150 °C

Procedure

To a stirred solution of 5-((4-bromo-5-fluoro-2-methoxyphenoxy)methyl)-2-methoxypyridine (4.57 g, 13.36 mmol) in N,N-dimethylformamide (50 mL) was added copper(I) cyanide (3.59 g, 40.07 mmol). The mixture was heated to 150° C. After 16 h, the mixture was allowed to cool to room temperature and was diluted with dichloromethane. The mixture was filtered through Celite. The filtrate was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. Chromatographic purification (Combi-Flash, 80 g SiO2 column, 1-5% methanol/dichloromethane elute) afforded 3.25 g (84%) of 2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzonitrile as an off-white solid.

Workup

temperatureto cool to room temperature
filtrationThe mixture was filtered through Celite
washThe filtrate was washed with water and brine
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customChromatographic purification (Combi-Flash, 80 g SiO2 column, 1-5% methanol/dichloromethane elute)

Sources & evidence

ORD record: ord-67c012121d214ae4a878745daba83a7c
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067914B1

Reaction notes

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