Ammonium Chloride → Benzo[b][1,8]naphthyridin-2(1H)-one

Temperature

-78 °C

To a solution of THF (15 mL) and LDA (2M in THF, 15.9 mmol, 7.95 mL), cooled to −78° C., was slowly added a solution of di-t-butyl succinate (15.9 mmol, 3.28 g) in THF (3.0 mL). After 15 minutes at −78° C. 3-Formyl-2-pivaloylaminoquinoline (1.92 g, 7.50 mmol) dissolved in THF (10 mL) was added. The clear yellow solution was stirred at −78° C. for 15 minutes and then allowed to warm to room temperature. The solution was poured into saturated aqueous ammonium chloride (200 mL) and extracted with dichloromethane (2×100 mL). The organic phase was dried (MgSO4) and evaporated in vacuo. The crude product of diastereomeric alcohols was heated to reflux for 24 hours in a mixture of THF (5 mL) and HCl (3M, aqueous) and then poured into water (100 mL) and neutralized with K2CO3. The tan precipitate was washed with water (2×25 mL) and dried in vacuo overnight. The crude product (1.60 g) was heated in acetonitrile (50 mL) and filtered while hot. The product was washed with ether (2×25 mL) and dried in vacuo to give 1.50 g (79%) of a material judged to be 61% pure according to HPLC (260 nm).

1. additionwas added
2. temperatureto warm to room temperature
3. extractionextracted with dichloromethane (2×100 mL)
4. dry with materialThe organic phase was dried (MgSO4)
5. customevaporated in vacuo
6. temperatureThe crude product of diastereomeric alcohols was heated
7. temperatureto reflux for 24 hours in a mixture of THF (5 mL) and HCl (3M, aqueous)
8. additionpoured into water (100 mL)
9. washThe tan precipitate was washed with water (2×25 mL)
10. customdried in vacuo overnight
11. temperatureThe crude product (1.60 g) was heated in acetonitrile (50 mL)
12. filtrationfiltered while hot
13. washThe product was washed with ether (2×25 mL)
14. customdried in vacuo

ORD record

ord-a1697e3bd7af4efb965a8ce365f59717

Source dataset

uspto-grants-2003_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06632919B1