Methyl chlorodifluoroacetate → 6-Methoxy-3-nitro-2-(trifluoromethyl)pyridine

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Reaction Steps

2-Chloro-6-methoxy-3-nitropyridine (5 g) was heated with Cul (6.05 g), KF(anhydrous, 3.0 g), methyl 2-chloro-2,2-difluoroacetate(6.8 ml) in DMF (28 ml) at 130° C. for 8 hrs. After cooling, it was poured into 1:9 mixture of NH4OH/NH4Cl(100 ml), stirred until homogeneous and extracted with Ethyl acetate. The organic layer were combined, washed with brine and dried (MgSO4), The flash column chromatography (SiO2, 1˜3% EtOAc in heptane) yielded 3.90 g (65%). 1H NMR (CDCl3) δ 4.02, 6.96, 8.10; IR (liq.) 2389 (w), 2254 (w), 2196 (w), 2163 (w), 2017 (w), 1605 (s), 1586 (s), 1538 (s), 1482 (s), 1340 (s), 1290 (s), 1261 (s), 1205 (s), 1180 (s), 1155 (s) cm−1 Anal. Calcd for C7H5F3N2O3: C, 37.85; H, 2.27; N, 12.61; F, 25.66. Found: C, 37.68; H, 2.29; N, 12.30.

Provenance & Evidence