4-Fluorophenol → Methyl 6-(4-fluorophenoxy)-5-methylnicotinate

HRID 715403Notes

Reaction equation

F[C:2]1[C:11]([CH3:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:2]2[C:11]([CH3:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=2)=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of methyl 6-fluoro-5-methylnicotinate (2.40 g, 14.2 mmol, Step-1 of Amine-36), 4-fluorophenol (2.39 g, 21.3 mmol), and potassium carbonate (3.92 g, 28.4 mmol) in DMF (45 mL) is stirred at 90° C. for 3 hours. After cooling to rt, the mixture is filtered through a pad of Celite and rinsed with EtOAc (200 mL). The filtrate is washed with water (200 mL) and brine (200 mL), and the organic layer is dried over sodium sulfate. After filtration, and the filtrate is concentrated in vacuo. The residue is purified by chromatography on silica gel eluting with n-hexane/EtOAc (20:1) to give 3.46 g (93% yield) of the title compound as white solid.

Workup

temperatureAfter cooling to rt
filtrationthe mixture is filtered through a pad of Celite
washrinsed with EtOAc (200 mL)
washThe filtrate is washed with water (200 mL) and brine (200 mL)
dry with materialthe organic layer is dried over sodium sulfate
filtrationAfter filtration
concentrationthe filtrate is concentrated in vacuo
customThe residue is purified by chromatography on silica gel eluting with n-hexane/EtOAc (20:1)

Sources & evidence

ORD record: ord-75bfb6aa46234c3a86a928f62177c602
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187475B2

Reaction notes

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