Sodium hydride → 4-Fluoro-2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-pyridine

Participants

Reaction Steps

2-(Tetrahydro-2H-pyran-2-yl-oxy)ethanol (731 mg, 679 μL, 5.00 mmol) was suspended in anhydrous THF and NaH (60% dispersion in mineral oil, 240 mg, 6.0 mmol) was added portionwise, resulting in evolution of gas and the reaction stirred at room temp. After 15 min, a solution of 2,4-difluoropyridine (690 mg, 6.00 mmol) in anhydrous THF (2 mL) was slowly added. After stirring for 2 h, the reaction was partitioned between H2O and EtOAc. The organic layer was separated, and the aqueous extracted again with EtOAc. The combined organics were dried over MgSO4, concentrated in vacuo and subjected to FCC, eluting with 0-30% EtOAc/cyclohexane, to afford the title compound as a colourless oil (633 mg, 43%). LCMS (Method 3) Rt 3.57 min, m/z 264.2 [M+Na].

Provenance & Evidence