Phosphoric Acid → 4-Methyl-5-fluoro-6-methoxy-8-nitroquinoline

Participants

Reaction Steps

To a hot (92°), stirred mixture of 54.4 g (0.292 mol) of 4-amino-2-fluoro-5-nitroanisole (XIII), 50.2 g (0.218 mol) of arsenic pentoxide, and 300 mL of 88% phosphoric acid was added 24.5 g (0.349 mol) of methyl vinyl ketone, during 0.5 hour. The reaction mixture was heated at 95° for 2.5 hours, cooled, diluted with 2.0 L of ice-water, then basified with 700 mL of concentrated ammonium hydroxide. The solid which separated was collected on a filter, washed with water (4×1.0 L), then air dried; yield, 140.6 g. The material was extracted with chloroform (2.0 L). The extract was concentrated to 500 mL then chromatographed on a column of silica gel (900 g) using chloroform as the eluent. The fractions containing product were combined then concentrated in vacuo to a solid; yield, 21.8 g (31.6%). The product was suitable for further transformation. Additional material (40.2 g) was obtained from a similar run and a scouting run.

Provenance & Evidence