Sodium hydride → trans-Methyl 2-[6-(trifluoromethyl)pyridin-3-yl]cyclopropanecarboxylate

Participants

Reaction Steps

To a vigorously stirring mixture of NaH (31.0 mg, 1.16 mmol) in DMSO (5 mL) at ambient temperature under an argon (g) atmosphere was added (CH3)3S(I)O (248 mg, 1.12 mmol) in small portions over ca. 1 min. Following complete addition, the reaction was stirred for 20 min. A DMSO (1 mL) solution of 26A (200 mg, 0.870 mmol) was added dropwise over ca. 1 min. The reaction was left to stir for 5 h then quenched with H2O (25 mL) and extracted into EtOAc (3×30 mL). The combined organics were washed with H2O (1×15 mL), brine (15 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was subjected to flash chromatography (SiO2-12 g; gradient elution: 0.25% MeOH/DCM for 3 min then 0.25-4% MeOH/DCM over 14 min at 25 mL/min) to afford 22.0 mg 26B (10% yield). m/z (ES+) M+1=246.1; HPLC tR=1.09 min. 1H NMR (500 MHz, CDCl3) δ 8.54 (d, J=1.8 Hz, 1H), 7.59 (d, J=8.2 Hz, 1H), 7.55-7.46 (m, 1H), 3.75 (s, 3H), 2.60 (ddd, J=9.6, 6.1, 4.1 Hz, 1H), 2.00 (ddd, J=8.6, 5.6, 4.1 Hz, 1H), 1.73 (dt, J=9.2, 5.1 Hz, 1H), 1.38 (ddd, J=8.6, 6.4, 5.1 Hz, 1H).

Provenance & Evidence