Water → tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate

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Reaction Conditions

Reaction Steps

An alternative procedure for the preparation is as follows: To a 3-necked flask equipped with stirrer, nitrogen inlet and internal thermometer was charged with 3-amino, 6-bromoisoquinoline (6.0 g, 20.0 mmol), 2-(2′,6′-dimethoxybiphenyl)dicyclohexylphosphine (S-Phos) (2.0 g 3.0 mmol), thoroughly freshly degassed DME (200 mL), water (40 mL), and Cs2CO3 (46.2 g, 142.0 mmol). The suspension was placed under nitrogen in a pre-heated oil bath at 86° C. Meanwhile, a solution of 1-BOC-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (10.8 g, 36.0 mmol) in degassed DME (30 mL) was prepared and stored under nitrogen. When the internal temperature of the suspension had reached 84° C., the Pd2(dba)3 (2.8 g, 3.0 mmol) was added, and quickly followed by dropwise addition of the pyrazole boronate solution (via syringe over 5 min). The resulting bi-phasic dark orange solution was stirred at 84° C. for 20 mins. The flask was then placed in an ice bath to cool rapidly. Once at ambient temperature, the mixture was filtered to remove inorganic substance, washed with water (2×25 mL). Upon reduction of the solution volume via evaporation the solid product was filtered and collected. The light yellow product was washed with ethyl ether 3 time (20 ml) to give a pale yellow solid product. Yield: 6.1 g, 98.4%.

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