Isatoic Anhydride → 1-[3-(2-chloro-4-methoxyphenoxy)propyloxymethyl]-4-hydroxy-2(1H)-quinolinone

Participants

Reaction Conditions

Reaction Steps

A solution of 2-chloro-4-methoxyphenol (15.5 gm) in DMF (20 ml) was added to a suspension of 60% sodium hydride (4 gm) in DMF (10 ml). To the resulting solution there was added a solution of 3-chloropropyl benzoate (15.5 gm) in DMF (20 ml). The solution was heated at 80° C. for 20 hrs, then diluted with ethyl acetate, then washed with water then dried and then evaporated. The crude product was dissolved in a 1:1 mixture of methanol/THF (40 ml) to which 10% sodium hydroxide (50 ml) was added. The mixture was refluxed for 3 hrs, then diluted with ethyl acetate, then washed with water and then evaporated. The crude product was purified by chromatography on silica gel using 40% ethyl acetate in hexane as the eluting solvent. The product was then dissolved in dichloroethane (40 ml) containing paraformaldehyde (2.25 gm). The solution was cooled in an ice bath and a stream of HCl gas was bubbled through the solution for 3.5 hrs. The solution was then dried over magnesium sulfate and the solvent was then removed under reduced pressure. Following the procedure set forth in Steps (2) to (4) of Preparation A, the resulting 3-(2-chloro-4-methoxyphenoxy) propyloxymethyl chloride was reacted with isatoic anhydride to give 1-[3-(2-chloro-4-methoxyphenoxy)-propyloxymethyl]-4-hydroxy-2(1H)-quinolinone. That the expected product was obtained was confirmed by the spectral data: MS: m/e 389 (M·+); NMR (DMSO): δ1.9 (t, 2H, CH2), 3.65 (t, 2H, CH2O), 3.70 (s, 3H, OCH3), 3.90 (t, 2H, CH2O), 5.65 (s, 2H, NCH2O), 5.84 (s, 1H, =CH).

Provenance & Evidence