Sodium Hydroxide → tert-butyl (3R)-3-(4-(1-methyl-5-(2H-tetrazol-5-yl)-1H-pyrazol-4-yl)-N-(3-methylpyridin-2-yl)benzamido)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a round-bottom flask charged with a stir bar was added Preparation 24, tert-butyl (3R)-3-{(3-methylpyridin-2-yl)[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl]amino}piperidine-1-carboxylate (1.53 g, 2.93 mmol) and Preparation 22, 5-(4-iodo-1-methyl-1H-pyrazol-5-yl)-2H-tetrazole (674 mg, 2.44 mmol). To this was added dioxane (12.2 mL) and aqueous NaOH (4.07 mL, 3M solution, 12.2 mmol). The reaction mixture was heated to 70° C. under nitrogen atmosphere for 30 min. To a microwave vial was added the Pd(OAc)2 (34.3 mg, 0.153 mmol) and Catacxium A (123 mg, 0.342 mmol). The atmosphere was exchanged for nitrogen, and toluene was added. The catalyst was stirred at room temperature for 15 min, until a bright yellow slurry formed. At this point, the catalyst was added to the reaction mixture, and the temperature was adjusted to 100° C. The reaction mixture was stirred for 3 h at 100° C. After complete consumption of the starting material, the reaction was concentrated under reduced pressure. H2O (10 mL) was added. The reaction mixture was extracted with MTBE (3×25 mL). The aq. phase was cooled to 0° C., and 1M HCl was added dropwise to form a precipitate which was collected via suction filtration and dried in vacuo to obtain tert-butyl (3R)-3-(4-(1-methyl-5-(2H-tetrazol-5-yl)-1H-pyrazol-4-yl)-N-(3-methylpyridin-2-yl)benzamido)piperidine-1-carboxylate (1.2 g, 90%).

Provenance & Evidence