Sodium hydride → HCID 68312825, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-hydroxypiperidine-1-carboxylic acid tertbutyl ester (176 mg, 0.88 mmol) in toluene (3 mL) was added NaH (60% in mineral oil, 35 mg, 0.88 mmol) and the mixture was heated at 70° C. for 15 min. After cooling to RT, 8-bromo-2-pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (200 mg, 0.58 mmol), Pd2 dba3 (11 mg, 0.001 mmol) and tertbutylXantphos (20 mg, 0.08 mmol) were added and the mixture was heated at 95° C. for 18 h. The reaction mixture was then partitioned between EtOAc and brine and the aqueous phase was further extracted with EtOAc (×3). The combined organic layers were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% 2M NH3/MeOH in DCM followed by Si-PCC, gradient 0-10% 2M NH3/MeOH in EtOAc) affording 3-(2-Pyridin-2-yl-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-8-yloxy)piperidine-1-carboxylic acid tertbutyl ester as a colorless oil, taken forward in the next step without further purification. LCMS: RT 2.68 min [M+H]+ 463.2

Provenance & Evidence