Trimethylsilylacetylene → Methyl 1-(3-fluoro-4-(2-(trimethylsilyl)ethynyl)benzyl)azetidine-3-carboxylate

Participants

Reaction Steps

Methyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate (25.00 g, 82.7 mmol), copper (I) iodide (3.14 g, 16.5 mmol), (trimethylsilyl)acetylene (81.9 mL, 579 mmol), bis(triphenylphosphine)palladium(II) chloride (5.81 g, 8.27 mmol), and Hunig's base (115 mL, 662 mmol) were combined in a sealable tube along with 100 mL THF. The tube was sealed and heated to 80 deg. C. under vigorous stirring for 24 h. The mixture was then cooled to room temperature, filtered, and evaporated. The resulting oil was purified by Biotage (75 L, 0-50% EtOAc/hexanes), affording methyl 1-(3-fluoro-4-(2-(trimethylsilyl)ethynyl)benzyl)azetidine-3-carboxylate as a transparent brown oil. MS (ESI) m/z: Calculated: 319.1; Observed: 320.1 (M++1).

Provenance & Evidence