Ammonia → HCID 59204976, compound

A mixture of 1-(2-fluoro-4-nitrophenyl)piperidin-4-one (compound of Reference Example 26; 5.00 g, 2.10 mmol), methylamine hydrochloride (2.83 g, 4.20 mmol), titanium tetraisopropoxide (11.9 g, 4.20 mmol), triethylamine (4.25 g, 4.20 mmol) and ethanol (25 ml) was stirred at room temperature for 16 hours under argon atmosphere. Sodium borohydride (1.58 g, 4.20 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 7 hours. 2.8N aqueous ammonia (25 ml) was added to the reaction mixture at 0° C., and the mixture was stirred for 30 minutes. The reaction mixture was filtered, and the filtrate was extracted with dichloromethane. 2N aqueous hydrochloric acid was added to the organic layer, and the mixture was stirred. The water layer was adjusted to pH=12 by addition of 2N aqueous sodium hydroxide and extracted with dichloromethane. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (2.12 g, 40%) as a yellow-brown liquid.

1. stirringthe mixture was stirred at room temperature for 7 hours
2. stirringthe mixture was stirred for 30 minutes
3. filtrationThe reaction mixture was filtered
4. extractionthe filtrate was extracted with dichloromethane
5. addition2N aqueous hydrochloric acid was added to the organic layer
6. stirringthe mixture was stirred
7. additionThe water layer was adjusted to pH=12 by addition of 2N aqueous sodium hydroxide
8. extractionextracted with dichloromethane
9. washThe organic layer was washed with water and saturated brine
10. dry with materialdried over anhydrous sodium sulfate
11. customThe solvent was evaporated under reduced pressure

ORD record

ord-e5da9e1c9469409fb084a6bef21b35f8

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07671058B2