Pyridine → 3-methoxy-N-[1-(methoxy-methyl-carbamoyl)-cyclopropyl]-2-methyl-benzamide

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Reaction Steps

A mixture of 5-(3-methoxy-2-methyl-phenyl)-6-oxa-4-aza-spiro[2.4]hept-4-en-7-one (VII, R1=2-Me-3-MeO—Ph, R2=R3=—(CH2)2—, 1.90 g, 8.2 mmol), N,O-dimethylhydroxylamine hydrochloride (0.96 g, 9.9 mmol), pyridine (0.80 mL, 9.9 mmol) and methylene chloride (30 mL) was stirred at room temperature for 1 week. The mixture was diluted with ethyl acetate (150 mL), washed with 5% aqueous HCl (2×50 mL) and saturated aqueous NaHCO3 (2×50 mL), and dried. Removal of the solvent afforded a crude product (2.54 g) as a syrup. The crude product was purified by flash chromatography on a silica gel (75 g) column eluted sequentially with 0, 20, 40, 60, 80, 100% ether in hexanes (200 mL of each) and ethyl acetate (500 mL) to afford 3-methoxy-N-[1-(methoxy-methyl -carbamoyl)-cyclopropyl]-2-methyl-benzamide (1.67 g, 69%) as a white solid, mp 173-175° C. 1H NMR (CDCl3) δ(ppm): 1.15 (m, 2H), 1.53 (m, 2H), 2.23 (s, 3H), 3.22 (s, 3H), 3.69 (s, 3H), 3.82 (s, 3H), 6.67 (s, 1H), 6.86 (d, J=7.9 Hz, 1H), 6.90 (d, J=7.9 Hz, 1H), 7.13 (t, J=7.9 Hz, 1H); 13C NMR (CDCl3) δ12.3, 15.1, 33.6, 35.1, 55.6, 61.0, 111.4, 118.6, 124.9, 126.5, 137.4, 157.9, 170.3, 170.9. Calculated for C15H20N2O4: C, 61.63; H, 6.90; N, 9.58. Found: C, 61.24; H, 6.75; N, 9.30.

Provenance & Evidence