Triisopropyl borate → 2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid

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Reaction Conditions

Reaction Steps

Place tetrahydrofuran (28.0 mL) in a 100 mL round-bottom flask equipped with a temperature probe, a magnetic stirrer, and a septum and put under a nitrogen atmosphere. Add 3-bromo-2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole (Preparation 1, 1.44 g, 5.18 mmol) and triisopropyl borate (3.10 mL, 13.5 mmol). Cool the mixture to −78° C. using a dry ice/acetone bath. Add 1.4M n-butyllithium in hexanes (8.80 mL, 12.4 mmol) dropwise via a syringe pump over 10 min keeping the temperature below −40° C. Remove the dry ice/acetone bath and allow the reaction mixture to warm to room temperature. Add saturated aqueous ammonium chloride (10 mL) and extract with chloroform (2×1 00 mL). Combine the organic layers, dry over solid sodium chloride, and remove the solvent under reduced pressure to afford an oil. Purify the oil by normal phase flash chromatography (120 g Biotage KP-Sil 40 L: 100% ethyl acetate in hexanes for 25 min, 0-10% methanol in ethyl acetate in ramp over 15 min, then 10% methanol in ethyl acetate) to yield the title compound (910 mg, 73%). MS ES+ m/e 244 (M+1).

Provenance & Evidence