Sodium hydride → 4-(4-Bromo-3-fluorophenoxy)-2-methylpyridine 1-oxide

HRID 2176845Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[H-].[Na+].[N+]([C:15]1[CH:16]=[C:17]([CH3:22])[N+:18]([O-:21])=[CH:19][CH:20]=1)([O-])=O>CN1CCCC1=O.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:15]2[CH:20]=[CH:19][N+:18]([O-:21])=[C:17]([CH3:22])[CH:16]=2)=[CH:4][C:3]=1[F:9]

Participants

Conditions

Temperature: 180 °C

Procedure

To a room temperature solution of 4-bromo-3-fluorophenol (6 g, 31.41 mmol) in N-methylpyrrolidone (20 ml) was added sodium hydride (1.34 g, 56 mmol, 60% in mineral oil) portionwise. After stirring for 10 minutes 4-nitro-2-picoline N-oxide (5.6 g, 36.12 mmol) was added. The reaction mixture was heated at 180° C. for 60 minutes under microwave irradiation. After cooling to room temperature the mixture was diluted with EtOAc (250 ml) and washed with water (250 ml). The solution was then extracted with additional EtOAc (2×150 ml) The combined organic extracts were dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM to DCM/MeOH(NH3) up to 2% as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate 13 (3.61 g, 39%).

Workup

additionwas added
temperatureAfter cooling to room temperature the mixture
washwashed with water (250 ml)
extractionThe solution was then extracted with additional EtOAc (2×150 ml) The combined organic extracts
dry with materialwere dried (Na2SO4)
customthe solvent evaporated in vacuo
customThe crude product was purified by column chromatography (silica gel; DCM to DCM/MeOH(NH3) up to 2% as eluent)
customThe desired fractions were collected
customevaporated in vacuo

Sources & evidence

ORD record: ord-42c91ddb85de4f7b8baadf39d3c3032f
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067891B2

Reaction notes

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