Hydrochloric Acid → 1H-indazol-1-ylacetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of indazole (1.0 g, 8.3 mM) in methanol (10 μl) are added 28% solution of sodium methoxide in methanol (3.53 ml, 18.26 mmole) and bromoacetic acid (1.41 g, 9.96 mmole), and the mixture is heated to reflux for 2 hr. After addition of the same amount of sodium methoxide and bromoacetic acid, the mixture is heated to reflux for another 1 hr. This procedures of-addition are repeated two more times and the mixture is cooled to 0° C. After addition of ethyl acetate, the mixture is adjusted to pH 5 with 1N HCl. The organic layer is taken and the aqueous layer extracted with ethyl acetate. Each organic solution is washed with a brine, dried over anhydrous magnesium sulfate and concentrated. The residue, when purified with column chromatography (SiO2, ethyl acetate→ethyl acetate/acetic acid/water, (40:1:1)→(30:1:1)→(8:1:1)), gives 1-carboxymethylindazole (487 mg, yield 33%). 1H NMR (DMSO) δppm: 5.27 (s, 2H), 7.16(dd, J=7.0 Hz, J=8.0 Hz, 1H), 7.39(dd, J=7.0 Hz, J=8.0 Hz, 1H), 7.64(d, J=8.0 Hz, 1H), 7.77(d, J=8.0 Hz, 1H), 8.09(s, 1H).

Provenance & Evidence