(3-Methoxyphenyl)boronic acid → ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

Participants

Reaction Steps

A suspension of 3-methoxyphenylboronic acid (30 mg, 0.2 mmol), Cu(OAc)2H2O (2 mg, 5 mol %), 3 Å molecular sieves (75 mg) in 1 mL of CH2Cl2 were stirred at room temperature for 5 min. Ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate hydrochloride 5c (42 mg, 0.1 mmol) was added to the reaction and mixture was stirred at room temperature for 24 h. The reaction was diluted with methanol, filtered and subjected to reverse-phase HPLC purification (2-50% CH3CN—H2O gradient, with 0.05% TFA, 15 min) to give pure ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro -1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate. LC-MS: m/z [M+H]+ 490.0, retention time 2.61 min (10-90% CH3CN—H2O gradient, with 0.05% TFA, 5 min).

Provenance & Evidence