Phosphorus oxychloride → 3-Quinolinecarboxylic acid, 4-chloro-8-methoxy-, ethyl ester

A stirred mixture of ethyl 4-hydroxy-8-methoxyquinoline-3-carboxylate, 66.63 g (0.269 mole) and phosphorous oxychloride (350 ml) was warmed until all the solid had dissolved and then heated at reflux temperature for two hours. After cooling to below 100° C. the mixture was concentrated in a rotary evaporator. The residual oil was dissolved in 100 ml acetone and the solution poured onto an ice-water mixture (800 ml). The mixture was neutralized with 6 N sodium hydroxide solution and the solid product extracted successively with 450 ml, 250 ml and 100 ml portions of methylene chloride. The extracts were combined, washed with water, dried over anhydrous magnesium sulfate and concentrated to yield 68.16 g crude product. This crude product was dissolved in 500 ml hot toluene and filtered to remove a small quantity of insoluble material. The toluene solution was filtered through a bed of 250 g fluorisil followed by two liters of toluene and four liters of chloroform. The purified solution was concentrated to give 64.17 g of oil (89%) which crystallized to an off-white solid on cooling. The solid melted at 75°-77° C.

1. temperaturewas warmed until all the solid
2. dissolutionhad dissolved
3. temperatureheated
4. temperatureat reflux temperature for two hours
5. temperatureAfter cooling to below 100° C. the mixture
6. concentrationwas concentrated in a rotary evaporator
7. dissolutionThe residual oil was dissolved in 100 ml acetone
8. additionthe solution poured onto an ice-water mixture (800 ml)
9. extractionthe solid product extracted successively with 450 ml, 250 ml and 100 ml portions of methylene chloride
10. washwashed with water
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated
13. customto yield 68.16 g crude product
14. filtrationfiltered
15. customto remove a small quantity of insoluble material
16. filtrationThe toluene solution was filtered through a bed of 250 g fluorisil
17. concentrationThe purified solution was concentrated

ORD record

ord-8369daafd2564f97bd571732e2613eec

Source dataset

uspto-grants-1982_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04343804