Triethylamine → HCID 12056915, compound

Temperature

10 °C

A 50 mL round bottom flask equipped with a stir bar, thermocouple, and a reflux condenser was charged with (2R)-1-amino-1-(4-bromophenyl)propan-2-ol (480 mg, 2.09 mmol), triethylamine (222 mg, 0.3 mL, 2.19 mmol) and THF (10 mL). The reaction mixture was cooled to 10° C. 2,6-Difluorobenzoyl chloride (387 mg, 2.1 mmol) was added to the THF solution keeping the temperature <30° C. The reaction mixture was stirred at 25-30° C. for 2 hours. Dichloromethane (40 mL) and water (60 mL)were added and the phases were separated. The aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic extracts were washed with aq. 0.5 N HCl (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give crude amide, which was placed in a 50 mL round bottom flask equipped with a stir bar, thermocouple, and a reflux condenser. The residue was dissolved in dichloromethane (25 mL), and the reaction mixture was cooled to −78° C. (Diethylamino)sulfur trifluoride (337 mg, 0.28 mL, 2.09 mmol) was added to the dichloromethane solution keeping the temperature −70° C. The reaction mixture was allowed to warm to 25° C. while stirring over 16 h. The reaction mixture was poured into 50 g ice containing conc. ammonium hydroxide (5 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic extracts were washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give crude product as a mixture of diastereomers. Column chromatography gave two products (270 mg of (4S,5S) as an oil and 171 mg of (4S,5R) as an oil, 60% overall yield for the combined isomers over the two steps).

1. customA 50 mL round bottom flask equipped with a stir bar
2. customthe temperature <30° C
3. customthe phases were separated
4. extractionThe aqueous layer was extracted with dichloromethane (2×20 mL)
5. washThe combined organic extracts were washed with aq. 0.5 N HCl (50 mL) and brine (50 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give crude amide, which
10. customwas placed in a 50 mL round bottom flask
11. customequipped with a stir bar
12. customthe temperature −70° C
13. temperatureto warm to 25° C.
14. stirringwhile stirring over 16 h
15. customThe phases were separated
16. extractionthe aqueous layer was extracted with dichloromethane (2×50 mL)
17. washThe combined organic extracts were washed with brine (50 mL)
18. dry with materialdried over sodium sulfate
19. filtrationfiltered
20. concentrationconcentrated under reduced pressure
21. customto give crude product
22. additionas a mixture of diastereomers
23. customColumn chromatography gave two products (270 mg of (4S,5S) as an oil and 171 mg of (4S,5R) as an oil, 60%
24. customoverall yield for the combined isomers over the two steps)

ORD record

ord-1f4f3d40bc3d4c808f3cc68630498c70

Source dataset

uspto-grants-2003_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06573286B1