3,4-Dichloroaniline → 4-[(3,4-Dichlorophenyl)amino]-1,6-dihydro-1-methyl-6-oxo-3-pyridinecarboxylic acid

Temperature

-78 °C

A suspension of 4-chloro-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (161 mg, 0.86 mmol) was treated with lithium diisopropylamide (2.0 M solution in tetrahydrofuran-ethylbenzene-heptane, 0.45 mL, 0.9 mmol). The resultant solution was stirred for 30 min at ambient temperature under nitrogen and was then cooled to −78° C. This is solution A. In a separate flask, a solution of 3,4-dichloroaniline (147 mg, 1.21 mmol) in tetrahydrofuran (3.0 mL) was cooled to −78° C. and treated with lithium diisopropylamide (2.0 M solution in tetrahydrofuran-ethylbenzene-heptane, 1.2 mL, 2.4 mmol). The resultant solution was stirred for 30 min at −78° C. and was transferred to solution A (also at −78° C.) via cannula. The resultant reaction mixture was stirred for 30 min at −78° C. and was then warmed to ambient temperature for 2.5 h. The reaction was diluted with ethyl ether (10 mL) and filtered. The solid was washed with ether (10 mL). The filtrate and washings were discarded. The solid was partitioned between ethyl acetate (60 mL) and 1 N hydrochloric acid (20 mL). The organics were washed with water (2×20 mL) and brine (20 mL). The combined aqueous portion was further extracted with ethyl acetate (20 mL). All organics were combined and dried over magnesium sulfate and concentrated in vacuo to afford a brown-colored solid (234 mg), used in step B without further purification.

1. customalso at −78° C.
2. customThe resultant reaction mixture
3. temperaturewas then warmed to ambient temperature for 2.5 h
4. filtrationfiltered
5. washThe solid was washed with ether (10 mL)
6. customThe solid was partitioned between ethyl acetate (60 mL) and 1 N hydrochloric acid (20 mL)
7. washThe organics were washed with water (2×20 mL) and brine (20 mL)
8. extractionThe combined aqueous portion was further extracted with ethyl acetate (20 mL)
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated in vacuo

ORD record

ord-264e86016ad24cc4bc3230761fd6d4a3

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07273877B2