3-Fluorophenol → Ethyl 4-(3-fluoro-phenoxy)butanoate

HRID 84945Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[CH2:9]([O:11][C:12](=[O:17])[CH2:13][CH2:14][CH2:15]Br)[CH3:10].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][CH2:15][CH2:14][CH2:13][C:12]([O:11][CH2:9][CH3:10])=[O:17]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-fluorophenol (10.0 g, 89.2 mmol), ethyl-4-bromobutanoate (21.5 g, 110 mmol), potassium carbonate (17.3 g, 125 mmol) and 100 mL of N,N-dimethylformamide was stirred and heated at 100° C. under nitrogen for 16 hours. The reaction mixture was cooled and partitioned between ethyl acetate and water. The aqueous portion was separated and extracted with 2×50 mL of ethyl acetate. The combined organic extracts were washed with 3×50 mL of water and 1×50 mL of brine and dried over sodium sulfate. The organic solution was concentrated and the residue was purified via flash chromatography on a silica gel column (95:5 hexane:ethyl acetate) to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.18 (t, J=7.12 Hz, 3H) 1.91-2.00 (m, 2H) 2.44 (t, J=7.29 Hz, 2H) 4.00 (t, J=6.44 Hz, 2H) 4.07 (q, J=7.12 Hz, 2H) 6.71-6.82 (m, 3H) 7.25-7.34 (m, 1H); MS (DCI+) m/z 244.1 [M+NH4]+.

Workup

temperatureThe reaction mixture was cooled
custompartitioned between ethyl acetate and water
customThe aqueous portion was separated
extractionextracted with 2×50 mL of ethyl acetate
washThe combined organic extracts were washed with 3×50 mL of water and 1×50 mL of brine
dry with materialdried over sodium sulfate
concentrationThe organic solution was concentrated
customthe residue was purified via flash chromatography on a silica gel column (95:5 hexane:ethyl acetate)

Sources & evidence

ORD record: ord-4bea9f56cf884bd38367f8e07eabc1e0
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846951B2

Reaction notes

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