2-(4-fluorophenyl)cycloheptan-1-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step AAF (1): A mixture of cycloheptanone (1.0 g, 8.92 mmol), 1-bromo-4-fluorobenzene (0.874 g, 4.99 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.067 g, 0.116 mmol), sodium tert-butoxide (1.157 g, 11.68 mmol) and tris(dibenzylideneacetone)dipalladium (0) (0.049 g, 0.053 mmol) in THF (10 mL) was heated at 80° C. overnight. The crude product was purified by Prep-HPLC (Solvent A=10% MeOH-90% water-0.1% TFA, Solvent B=90% MeOH-10% water-0.1% TFA. Column: Phenomenex Luna 30×100 mm, S10, Flow rate: 40 ml/min, 45-100% B, 30 min) to obtain 2-(4-fluorophenyl)cycloheptanone (400 mg, 1.94 mmol, 22% yield). LC-MS (M+H)+=207.2. 1H NMR (400 MHz, methanol-d4) δ ppm 7.13-7.31 (m, 2 H) 6.91-7.08 (m, 2 H) 3.68-3.86 (m, 1 H) 2.58-2.76 (m, 1 H) 2.42-2.57 (m, 1 H) 1.85-2.13 (m, 5 H) 1.57-1.75 (m, 1 H) 1.35-1.57 (m, 2 H). The crude product was purified by Prep-HPLC (Solvent A=10% MeOH-90% water-0.1% TFA, Solvent B=90% MeOH-10% water-0.1% TFA. Column: Phenomenex Luna 30×100 mm, S10, Flow rate: 40 ml/min, 45-100% B, 30 min)