Diisopropylamine → 4-Chloronicotinic acid hydrochloride

To a solution of diisopropylamine (20.0 g) in tetrahydrofuran (200 ml) is added dropwise 1.6 M n-butyllithium/n-hexane solution under ice-cooling. The mixture is then stirred for 30 minutes under the same cooling conditions. The reaction mixture is cooled with dry ice-acetone, and thereto is added dropwise a solution of 4-chloropyridine (20.4 g) in tetrahydrofuran (100 ml). The mixture is then stirred for 20 minutes under the same cooling conditions. The resulting reaction solution is poured in crushed dry ice in a portion and then warmed to room temperature. The reaction solution is cooled with ice and basified by addition of sodium hydroxide, followed by concentration under reduced pressure. The resulting residue is dissolved in water and washed with dichloromethane. The aqueous layer is cooled with ice and acidified with conc. hydrochloric acid. The precipitates are collected by filtration and dried to give 4-chloronicotinic acid hydrochloride (21.4 g).

1. temperaturecooling
2. temperaturesame cooling conditions
3. stirringThe mixture is then stirred for 20 minutes under the
4. temperaturesame cooling conditions
5. customThe resulting reaction solution
6. temperatureThe reaction solution is cooled with ice
7. concentrationfollowed by concentration under reduced pressure
8. dissolutionThe resulting residue is dissolved in water
9. washwashed with dichloromethane
10. temperatureThe aqueous layer is cooled with ice
11. filtrationThe precipitates are collected by filtration
12. customdried

ORDレコード

ord-bce8909d0b5e40458370e4e1f9385f9e

出典データセット

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07737161B2