Triethylamine → HCID 53834887, compound

Using the methods of Lumma (J. Med. Chem., 1981, 24, 93-101), a suspension of DL-alanine ethyl ester hydrochloride (24.1 g, 157 mmol) in dichloromethane (200 mL) was treated with 16 mL of 10 N NaOH (160 mmol) and the mixture stirred 15 min. Anhydrous MgSO4 was added and the mixture stirred until a thick paste formed. The dichloromethane was decanted from the aqueous paste and further dried over anhydrous MgSO4. The organic solution was filtered, and concentrated to approximately 50 mL in volume. This was added to a solution of 2,5-difluoronitrobenzene (25 g, 157 mmol) in toluene (50 mL). The reaction was heated at reflux until the total volume was less than 50 mL. A reflux condenser was added to the reaction flask and the solution heated at reflux for 2 hours. After this time, triethylamine (22 mL, 158 mmol) was added and the reaction heated at reflux for an additional 1 hour. The reaction mixture was then cooled, diluted with chloroform and adsorbed on to silica. Chromatography through silica (20×4.5 cm i.d.) using a gradient of hexane to ethyl acetate afforded 17.4 g (43%) of N-(4-fluoro-2-nitrophenyl)alanine ethyl ester:

1. stirringthe mixture stirred until a thick paste
2. customformed
3. customThe dichloromethane was decanted from the aqueous paste
4. dry with materialfurther dried over anhydrous MgSO4
5. filtrationThe organic solution was filtered
6. concentrationconcentrated to approximately 50 mL in volume
7. temperatureThe reaction was heated
8. temperatureat reflux until the total volume was less than 50 mL
9. additionA reflux condenser was added to the reaction flask
10. temperaturethe solution heated
11. temperatureat reflux for 2 hours
12. temperaturethe reaction heated
13. temperatureat reflux for an additional 1 hour
14. temperatureThe reaction mixture was then cooled

ORD record

ord-2ec4be5ef7214904998baa2d8f807bc6

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06429207B1