Pyridinium chloride → 4-Hydroxydiclofenac lactam

Temperature

180 °C

The 2-[(2,6-dichloro-4-methoxyphenyl)amino]phenylacetic acid (0.1 mol) from example 22 was added in portions to a melt of 200 g of pyridine hydrochloride (1.75 mol) at 170° C. The mixture was heated at 180° C. for 3 h and poured onto 2000 ml of ice water while hot. The precipitated product was filtered off, washed with water, and dissolved in 1000 ml of ethyl acetate. The organic phase was washed with 200 ml of 1N HCl in water (2×100 ml) and evaporated to give N-(2,6-dichloro-4-hydroxyphenyl) oxindole. To a solution of 8 g of N-(2,6-dichloro-4-hydroxyphenyl)-oxindole in 200 ml of n-butanol were added 7 g of NaOH and 1 g of KOH, and the reaction mixture was refluxed for 24 h and evaporated in vacuo. The residue was dissolved in 700 ml of water and the aqueous solution was extracted with ether (2×200 ml), cooled to 0° C., and acidified with concentrated HCl. The precipitate was taken up in 300 ml of ether. The organic phase was washed with 30 ml of water, 0.5N NaHCO3 (5×80 ml), and 80 ml of 2N KHCO3 solution. The combined NaHCO3 extracts were cooled to 0° C. and acidified with 2N HCl, and the precipitate was dissolved in 200 ml of ether. The organic layer was washed with 30 ml of water and evaporated to yield 2-[(2,6-dichloro-4-hydroxyphenyl)amino]phenylacetic acid.

1. filtrationThe precipitated product was filtered off
2. washwashed with water
3. dissolutiondissolved in 1000 ml of ethyl acetate
4. washThe organic phase was washed with 200 ml of 1N HCl in water (2×100 ml)
5. customevaporated

ORD record

ord-1b7d62b723ed4fc3a3557646036a8170

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06355680B1