2-Indanone → HCID 24954056, compound

Temperature

2.5 °C

1,2-dichloroethane (118.8 L), sodium sulphate (19.3 kg) and ethyl 6-amino-1-ethyl-4-oxo-1,8-naphthyridine-3-carboxylate (3.6 kg) were added sequentially to the reactor at 25-30° C. under a nitrogen atmosphere and cooled to 0-5° C. 2-Indanone (1.80 kg) was added to the reaction mixture under stirring at 0-5° C., followed by slow addition of acetic acid (136.8 L) keeping temperature at 0-5° C. The reaction mixture was stirred at 0-5° C. for 10-15 minutes. 13.8 L of sodium triacetoxy borohydride solution (prepared at step 1) was added slowly in three installments of 4.6 L each at 0-5° C. and stirred at 0-5° C. for 2 h. Then, sodium sulphate (10.1 kg) and 2-indanone (878 g) were sequentially added to reaction mixture at 0-5° C. 8.0 L of the sodium triacetoxy borohydride solution (prepared at step 1) were slowly added to the reaction mixture at 0-5° C. and the reaction mixture was maintained at 0-5° C. for 10-12 h. The reaction progress was monitored by TLC for disappearance of starting material. After the completion of reaction (15 h), solvents were removed under vacuum below 60° C. and the reaction mass was cooled to 25-30° C. Dichloromethane (72.0 L) was added to reaction mixture with stirring at 25-30° C. and stirring was continued for 20-30 minutes. Then, reaction mixture pH was adjusted to 7-8 with aqueous sodium bicarbonate solution (prepared by dissolving 36 kg of sodium bicarbonate in 324 L of water) and the reaction mixture was stirred at 25-30° C. for 10-15 minutes. Two layers were allowed to separate over 15-20 minutes and then the organic layer was separated. Aqueous layer was washed with 36 L of dichloromethane twice and all organic layers were pooled, washed twice with water (2×36 L) and with aqueous sodium chloride solution (prepared by dissolving 7.2 kg of sodium chloride in 28.8 L of water); and finally dried over anhydrous sodium sulphate (1.8 kg) at 25-30° C. by stirring for 15-20 minutes. The solution was filtered through a Nutsche filter. The filtrate was transferred to a reactor and solvents were distilled under vacuum below 40° C.

1. customat 0-5° C
2. stirringThe reaction mixture was stirred at 0-5° C. for 10-15 minutes
3. stirringstirred at 0-5° C. for 2 h
4. temperaturethe reaction mixture was maintained at 0-5° C. for 10-12 h
5. customAfter the completion of reaction (15 h), solvents
6. customwere removed under vacuum below 60° C.
7. temperaturethe reaction mass was cooled to 25-30° C
8. additionDichloromethane (72.0 L) was added to reaction mixture
9. stirringwith stirring at 25-30° C.
10. stirringstirring
11. customThen, reaction mixture pH
12. stirringthe reaction mixture was stirred at 25-30° C. for 10-15 minutes
13. customto separate over 15-20 minutes
14. customthe organic layer was separated
15. washAqueous layer was washed with 36 L of dichloromethane twice
16. washwashed twice with water (2×36 L) and with aqueous sodium chloride solution (prepared by dissolving 7.2 kg of sodium chloride in 28.8 L of water)
17. dry with materialand finally dried over anhydrous sodium sulphate (1.8 kg) at 25-30° C.
18. stirringby stirring for 15-20 minutes
19. filtrationThe solution was filtered through a Nutsche
20. filtrationfilter
21. customThe filtrate was transferred to a reactor
22. distillationsolvents were distilled under vacuum below 40° C.

ORD record

ord-58790fd075c444e7897ca0172b200e8c

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133188B2