Triethylamine → (2S)-1,2,3,4-Tetrahydro-2-methylquinoxaline

Temperature

35 °C

A 1-L round bottomed flask containing (S)-2-(2-aminophenylamino)propane-1-ol (5.12 g, 30.8 mmol) was charged with acetonitrile (400 mL). The solution was concentrated partially in order to azeotropically dry the solution (ca. 100 mL of acetonitrile were removed). Triphenylphosphine (17.77 g, 67.8 mmol) was added, and once the triphenylphosphine had dissolved, carbon tetrabromide (22.47 g, 67.8 mmol) was added. The internal temperature gradually increased to a high of 35° C. After 10 min, triethylamine (18.89 mL, 136 mmol) was added. After 15 min, the reaction mixture was heated to 80° C. After 4 h, heating was discontinued and the reaction mixture stirred at rt overnight. The reaction mixture was diluted with aqueous sodium hydroxide and the mixture stirred at rt until hydrolysis of the iminophosphorane was complete. The mixture was extracted with dichloromethane. The dichloromethane extract was concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel. The product-containing fractions were concentrated to afford (S)-2-methyl-1,2,3,4-tetrahydroquinoxaline (1.9 g, 41%). MS (ESI, pos. ion) m/z 149 [M+1]+.

1. concentrationThe solution was concentrated partially in order
2. customto azeotropically dry
3. customthe solution (ca. 100 mL of acetonitrile were removed)
4. waitAfter 15 min
5. temperaturethe reaction mixture was heated to 80° C
6. waitAfter 4 h
7. temperatureheating
8. extractionThe mixture was extracted with dichloromethane
9. extractionThe dichloromethane extract
10. concentrationwas concentrated under reduced pressure
11. customThe crude product was purified by flash chromatography on silica gel
12. concentrationThe product-containing fractions were concentrated

ORD record

ord-bbca85857a624a8e9242737118dd01f1

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422281B2