DL-alanine → (2S)-2-propanamidopropanoic acid

Trimethylsilyl chloride (52.4 ml, 0.41 mol) was added dropwise to an ice-cooled solution of D,L-alanine (16.71 g, 0.188 mol) and triethylamine (57.5 ml, 0.41 mol) in dichloromethane (190 ml). Once addition was complete, the solution was stirred at room temperature for 1 h, followed by 1 h at 40° C. The solution was then cooled to −10° C., propionyl chloride (16.29 ml, 0.188 mol) was added dropwise over 15 minutes and, once addition was complete, the reaction was stirred at −10° C. for 2 h, then 16 h at room temperature, before cooling in an ice-bath. Water (100 ml) was added, the mixture was stirred for 15 minutes, then the phases separated. The aqueous layer was evaporated under reduced pressure and the residue triturated with acetone. The resulting solid was filtered off, and the filtrate concentrated under reduced pressure, to give an oil. This oil was purified by column chromatography using DCM:MeOH:0.88 NH3(aq) (89:10:1) as eluant, to give the title compound (20 g; containing 33% triethylamine).

1. additionOnce addition
2. waitfollowed by 1 h at 40° C
3. temperatureThe solution was then cooled to −10° C.
4. additiononce addition
5. stirringthe reaction was stirred at −10° C. for 2 h
6. temperature16 h at room temperature, before cooling in an ice-bath
7. stirringthe mixture was stirred for 15 minutes
8. customthe phases separated
9. customThe aqueous layer was evaporated under reduced pressure
10. customthe residue triturated with acetone
11. filtrationThe resulting solid was filtered off
12. concentrationthe filtrate concentrated under reduced pressure
13. customto give an oil
14. customThis oil was purified by column chromatography

ORD record

ord-2cd6994aa0584030b1a71739577c22eb

Source dataset

uspto-grants-2004_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06794387B2