2-Acetylbutyrolactone → 3-(2-Chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-Amino-3-benzyloxypyridine (formula-2) (20 grams) in toluene (40 ml) added 2-acetyl gammabutyro lactone (formula-3) (16.6 grams), stirred for 15 min and added phosphorus oxychloride (0.27 ml). The reaction mixture was refluxed for 12 hours and water was removed azeotropically. Then the reaction mixture was cooled to 70-80° C., added phosphorus oxychloride (11.9 ml) and then heated to 90-95° C. and stirred for 8 hr. The solvent was distilled off under reduced pressure and concentrated hydrochloric acid (70 ml) was added to the reaction mixture followed by toluene (100 ml) and stirred at 65-70° C. for 9 hours. The reaction mixture was cooled to 0-5° C. and the solid formed was filtered, washed with toluene and acetic acid. The wet solid was taken in autoclave along with acetic acid (110 ml), added Pd/C and applied 3.0-3.5 kg/cm2 hydrogen pressure. The reaction mixture was heated to 50-60° C., stirred for 8 hrs, then cooled to 25° C. and quenched with water. The reaction mixture was filtered and the pH of the filtrate was adjusted to 11 using aqueous sodium hydroxide solution. Extracted the reaction mixture with ethyl acetate. The ethyl acetate layer was treated with basic carbon, filtered and distilled off under reduced pressure. The solid formed was taken in cyclohexane (45 ml) and stirred for 60 min at 25° C. The solid was filtered, washed with cyclohexane and dried to provide the title compound.

Provenance & Evidence