Dichloromethane → Tert-butyl 4-(4'-methoxybiphenyl-4-ylcarbamoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

[1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (8.3 mg, 0.010 mmol) was added to a mixture of tert-butyl 4-(4-bromophenylcarbamoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate (100 mg, 0.204 mmol, prepared as in Example 2, Step 1), (4-methoxyphenyl)boronic acid (61.9 mg, 0.407 mmol) and sodium carbonate (42.4 mg, 0.407 mmol) in toluene (4 mL), 1,4-dioxane (1 mL), and water (1 mL). The reaction mixture was heated to 80° C. for 3 h. Upon cooling to room temperature, the reaction mixture was filtered though Celite®, concentrated under reduced pressure, and purified by HPLC (10 to 90% MeCN/0.1% TFA in H2O/0.1% TFA gradient). This gave 114.9 mg (89%, ˜90% pure) of the TFA salt of the desired product as a thick, brownish oil. LC-MS: RT=8.69 min, [M+H]+=519.2.

Provenance & Evidence