Chlorotrimethylsilane → 1,1-Dimethylethyl 3-(2-quinolinyl)-1-azetidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of Zn dust (1.70 g, 26.0 mmol) in THF (5 mL) under an Argon atmosphere, 1,2-dibromoethane (250 μl) was added at rt. The resulting mixture was heated at 65° C. for 3 min and allowed to cool to rt. TMSCl (350 μl) was then added and the mixture was stirred at rt for 30 min. tert-Butyl 3-iodoazetidine-1-carboxylate (5.70 g, 20.0 mmol) in THF (15 mL) was then added slowly and the resulting mixture was allowed to stir at rt for 45 min. A solution of Pd2(dba)3 (183 mg, 0.200 mmol) and trifurylphosphine (186 mg, 0.801 mmol) in THF (5 mL) were stirred at rt for 10 min under an Argon atmosphere and the resulting mixture was added to the organozinc reagent prepared, followed by addition of 2-bromoquinoline (5.00 g, 24.0 mmol). The mixture was then heated at 65° C. for 48 h under Argon. The reaction mixture was allowed to cool to rt and filtered through a pad of diatomaceous earth. The filtrate was concentrated and the residue obtained was purified by flash column chromatography on silica gel (0:1-1:0% EtOA/heptanes) to obtain tert-butyl 3-(quinolin-2-yl)azetidine-1-carboxylate.

Provenance & Evidence