5-Pyrimidinylboronic acid synthesis

Yield:109299-78-7 44%

Reaction Conditions:

Stage #1:5-bromopyrimidine with n-butyllithium;Triisopropyl borate in tetrahydrofuran;hexane;toluene at -70 - -20; for 0.5 h;
Stage #2: with hydrogenchloride;water in tetrahydrofuran;hexane;toluene at -20 - 20;
Stage #3: with potassium hydroxide in water; pH=5.5

Steps:

5-Pyrimidineboronic acid; "BuLi (3.02 ml, 2M solution in hexane, 7.55 mmol) was added dropwise to a stirring solution of 5-bromopyrimidine (1 g, 6.29 mmol) and triisopropylborate (1.46 ml, 7.55 mmol) in anhydrous toluene (16 ml) and anhydrous THF (4 ml) at-70°C under a nitrogen atmosphere. The reaction mixture was stirred at-70°C for 30 mins and then removed from the cold bath. When the internal temp. reached-20°C, the reaction was quenched by the dropwise addition of 2M HCI (10 ml). The mixture was allowed to warm to RT and then separated. The aqueous phase was taken to pH 5.5 with 2M KOH and extracted into THF (3 x 25 ml). The combined organic extracts were dried (MgS04), filtered and concentrated in vacuo to provide a colourless solid. The solid was slurried in acetonitrile (2 ml), collected by filtration and dried on the sinter to give the target boronic acid as a brilliant white solid (340 mg, 44%). 8H(MeOD; 250MHz) 8.98 (2H, s), 9.14 (1H, s).

References:

ARAKIS LTD. WO2005/103019, 2005, A1 Location in patent:Page/Page column 16

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