1,1,3,3-Tetramethylguanidine → Methyl 2-acetoxy-3-(2-(methoxymethyl)-7-methyl-2H-indazol-5-yl)acrylate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 2-acetoxy-2-(diethylphosphoryl)acetate (4.89 g, 18.2 mmol) in tetrahydrofuran (25 mL) was added lithium chloride (0.74 g, 17.5 mmol). The reaction was stirred until dissolution was complete. The reaction was cooled to −78° C., and treated with tetramethylguanidine (2.20 mL, 17.5 mmol) to give a white suspension which was stirred for 10 min. To this was added 2-(methoxymethyl)-7-methyl-2H-indazole-5-carbaldehyde (3.10 g, 15.2 mmol) in one portion. After 10 min, the ice bath was concentrated and the reaction stirred overnight. The reaction was poured onto water/diethyl ether, and the layers separated. The ethereal was washed with water, then brine, dried over magnesium sulfate, and concentrated. Column chromatography gave recovered 2-(methoxymethyl)-7-methyl-2H-indazole-5-carbaldehyde (0.57 g, 18%) and the title compound (2.86 g, 59%) as a colorless oil. NMR shows a 3:2 ratio of Z and E isomers which were not separated. Major (Z isomer): 1H-NMR (CDCl3, 500 MHz) δ 2.25 (s, 3H), 2.62 (s, 3H), 3.40 (s, 3H), 3.71 (s, 3H), 5.69 (s, 2H), 6.88 (s, 1H), 7.09 (s, 1H), 7.72 (s, 1H), 8.10 (s, 1H). Mass spec.: 319.18 (MH)+. Minor (E isomer): 1H-NMR (CDCl3, 500 MHz) δ 2.35 (s, 3H), 2.62 (s, 3H), 3.40 (s, 3H), 3.85 (s, 3H), 5.69 (s, 2H), 7.32 (s, 1H), 7.38 (s, 1H), 7.78 (s, 1H), 8.14 (s, 1H). Mass spec.: 319.18 (MH)+.

Provenance & Evidence