Tetrahydrofuran → 4-[2-(3,5-Difluoro-benzyloxy)-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester

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Reaction Steps

3,5-Difluorobenzyl alcohol (227.5 μL, 2.01 mmol) was dissolved into 15 mL of anhydrous tetrahydrofuran and treated with sodium hydride (80.3 mg, 60% dispersion in mineral oil, 2.01 mmol). This was stirred under nitrogen for 15 minutes at ambient temperature, then the reaction was treated with 4-(2-chloro-pyrimidin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (I-1a) (500 mg, 1.67 mmol) in one portion. The resultant mixture was refluxed under nitrogen for 4 hours. After cooling to room temperature, the reaction was poured into water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (20 mL), then dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (silica gel, 1:1 ethyl acetate:hexanes) to afford 605.2 mg of the title product (I-1b).

Provenance & Evidence