4-Fluorophenol → Methyl 5-chloro-2-(4-fluorophenoxy)benzoate

HRID 1293218Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].[Cl:11][C:12]1[CH:13]=[CH:14][C:15](F)=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]>CN(C)C=O.CCOCC>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([O:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[C:16]([CH:21]=1)[C:17]([O:19][CH3:20])=[O:18]

Participants

Conditions

Temperature: 120 °C

Procedure

To a stirred solution of 4-fluorophenol (1.60 g, 14.3 mmol) and sodium hydride (0.34 g, 14.3 mmol) in N,N-dimethylforamide (30 mL) was added a solution of methyl 5-chloro-2-fluorobenzoate (2.70 g, 14.3 mmol) in N,N-dimethylforamide (30 mL) at 0° C. The resulting mixture was heated at 120° C. for 16 h. After cooling to room temperature, the mixture was diluted with ether (300 mL) and washed with water (150 mL×3). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (20:1) to afford 2.60 g (65%) of the title compounds as slight yellow oil: 1H-NMR (CDCl3) δ 7.88 (1H, d, J=2.8 Hz), 7.40 (1H, dd, J=8.8, 2.8 Hz), 7.06–6.85 (5H, m), 3.84 (3H, s).

Workup

temperatureAfter cooling to room temperature
washwashed with water (150 mL×3)
dry with materialThe organic layer was dried over magnesium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified
customby flush column chromatography on silica gel eluting with hexane/ethyl acetate (20:1)

Sources & evidence

ORD record: ord-448d7668b5944fa19368808e06f24727
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07238714B2

Reaction notes

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