Sodium hydroxide--water (1/1/1) → 3-bromo-2-fluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one

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Reaction Conditions

Reaction Steps

A mixture of 5-(4-bromo-3-fluorophenyl)pentanoic acid from step L2 (5.1 g, 18.54 mmol) in polyphosphoric acid (75 g, 18.5 mmol) was stirred at 145-150° C. for 3 h. After cooling to rt, the mixture was poured into ice, neutralized with 50% NaOH/water, and extracted with EtOAc/diethyl ether. The organic layer was dried over sodium sulfate and concentrated. The residue was purified via silica gel column chromatography (hexanes-8% EtOAc) to give 3-bromo-2-fluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-one (2.7 g, 10.5 mmol, 57% yield). LCMS (M+H)+=257.0. 1H NMR (500 HMz, chloroform-d) δ 7.98 (d, J=7.3 Hz, 1H), 6.99 (d, J=8.9 Hz, 1H), 2.93-2.89 (m, 2H), 2.77-2.73 (m, 2H), 1.95-1.88 (m, 2H), 1.87-1.81 (m, 2H).

Provenance & Evidence