Chlorotrimethylsilane → 2-Hydroxynicotinic acid

A suspension of 4.29 g (30 mM) of 2-oxo-1-pyrrolidineacetic acid, 2.20 ml (30 mM) of thionyl chloride, 2.32 ml (30 mM) of dimethylformamide, and 75 ml of dichloromethane was stirred with ice bath cooling for 11/4 hrs. A mixture of 4.60 g (20 mM) of 6-(4-aminophenyl)-1,2-dihydro-2-oxonicotinic acid, 140 ml of dichloromethane, 8.4 ml (60 mM) of triethylamine, and 7.6 ml (60 mM) of chlorotrimethylsilane was stirred at room temperature for 1 hr. The silylated pyridone solution was cooled with an ice bath and the cold solution of the acid chloride was added. The reaction mixture was stirred for 4 hrs with cooling and at room temperature for 18 hrs. The reaction mixture was evaporated to a wet solid. Ethanol was added, and the mixture was evaporated. The residue was treated with water and the solid filtered. The solid was washed with water, ethanol, and ether and dried to give 6.49 g of 6-[4-[2-oxo-1-pyrrolidinyl)acetylamino]-phenyl]-1,2-dihydro-2-oxonicotinic acid; mp <320°.

1. temperaturecooling for 11/4 hrs
2. stirringwas stirred at room temperature for 1 hr
3. stirringThe reaction mixture was stirred for 4 hrs
4. customThe reaction mixture was evaporated to a wet solid
5. additionEthanol was added
6. customthe mixture was evaporated
7. additionThe residue was treated with water
8. filtrationthe solid filtered
9. washThe solid was washed with water, ethanol, and ether
10. customdried

ORD record

ord-a3e1f707219c4227af91fbb2c5473e39

Source dataset

uspto-grants-1981_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04278681