Hydrochloric Acid → 3-Pyridinemethanol

Participants

Reaction Steps

A solution of 0.5 g of 2-isobutyramido-3-cyano-5-(bromoacetyl)pyridine and 1.25 g of 1(R)-methyl-2-(1H-indol-3-yl)ethyl amine in 50 ml of dry acetonitrile under nitrogen is stirred for 30 minutes at room temperature. The reaction mixture is made acidic with gaseous hydrochloric acid and then diluted with ether. The solution is concentrated and the residue redissolved in methanol. The solution is cooled in an ice bath and treated slowly with sodium borohydride (0.4 g) for one hour. The pH of the solution is adjusted to approximately 6 with acetic acid and extracted with CH2Cl2. The combined organic extracts are backwashed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product is dissolved in 15 ml of methanol and treated with 0.7 g of KOH. The reaction mixture is heated at reflux for 2 hours and then partially concentrated. The solution is diluted with water and extracted with CH2Cl2. The combined extracts are backwashed with saturated sodium chloride solution and dried with anhydrous magnesium sulfate prior to concentration. The residue is chromatographed on silica gel to give (R)-6-Amino-5-cyano-α-[[1(R)-methyl-2-(1H-indol-3-yl)ethyl)amino]methyl]-3-pyridinemethanol and (S)-6-Amino-5-cyano-α-[[(1-(R)-methyl-2-(1H-indol-3-yl)ethyl)amino]methyl]-3-pyridinemethanol.

Provenance & Evidence