8-Hydroxyquinoline → (trans)-Tert-butyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of quinolin-8-ol (3.50 g, 24.1 mmol) in 60 mL DMF was added cesium carbonate (23.6 g, 72.3 mmol), followed by (cis)-tert-butyl 3-fluoro-4-(methylsulfonyloxy)piperidine-1-carboxylate (8.24 g, 27.7 mmol). The reaction mixture was heated in a 100° C. sand bath and stirred 20 hours. The reaction mixture was cooled to ambient temperature, filtered through GF/F paper topped with compressed Celite, rinsed with DMF, and concentrated. The crude was purified on silica gel (Biotage 40M, 9:1 DCM:EtOAc until the product eluted, then 2:1 DCM:EtOAc) to give (trans)-tert-butyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate (0.701 g, 2.02 mmol, 42% yield). LC/MS ESI (+) m/z 347 (M+1) detected.

Provenance & Evidence