Sodium Hydroxide → 2-Chloro-1,6-naphthyridine

Temperature

70 °C

A mixture of phosphoryl trichloride (5.17 ml, 56.5 mmol) and 1,6-naphthyridin-2(1H)-one (112) (1.65 g, 11.29 mmol, Alfa Aesar) was stirred at 70° C. for 16 h. The reaction mixture was cooled to RT and was poured onto 150 g of ice carefully. EtOAc (50 mL) was added and the mixture was treated carefully with about 30 mL of 5 M NaOH until the final pH is persistently >10. The mixture was vigorously mixed, then transferred into a separatory funnel. The EtOAc layer was then separated and dried and re-suspended in 30 mL of DCM, the insoluble solids were filtered off. The filtrate was loaded onto a silica gel pad and flushed with 30% EtOAc in hexanes to give a solid after drying. The solid was initially white but changed color to yellow after drying on the high vacuum line over night. Yield; 1.19 g, 64%. The material (113) was used directly in the next step without any further purification.

1. temperatureThe reaction mixture was cooled to RT
2. additionThe mixture was vigorously mixed
3. customtransferred into a separatory funnel
4. customThe EtOAc layer was then separated
5. customdried
6. filtrationthe insoluble solids were filtered off
7. customflushed with 30% EtOAc in hexanes
8. customto give a solid
9. customafter drying
10. customafter drying on the high vacuum line over night
11. customThe material (113) was used directly in the next step without any further purification

ORD record

ord-7007f16cf82144508cde6d51a160adc0

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957073B2