Reacción #74299

Ecuación de reacción

p-toluoyl chloride

L-aspartic acid β-methyl ester hydrochloride

Et3N

Me3SiCl

→

amide

Rendimiento 91.0%

methyl 3-[(4-methylbenzoyl)amino]-4-oxopentanoate

Rendimiento 91.0%

Disolventes

CH2Cl2

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   Temperaturato warm to ambient slowly
3. 3
   workup.STIRRINGwith stirring for 16 hours
4. 4
   Lavadowashed with 1N HCl (500 mL), brine (500 ml)
5. 5
   Secadodried over Na2SO4

Procedimiento

To a suspension of L-aspartic acid β-methyl ester hydrochloride (250 g, 1.36 mol) in chilled (<5° C.) CH2Cl2 (4 L) was added Et3N (440 g, 4.35 mol) in a steady flow followed by a slow addition of Me3SiCl (324 g, 2.99 mol). The mixture was warmed to 25° C. and stirred for one hour, cooled again (<10° C.), and p-toluoyl chloride (205 g, 1.36 mol) was added dropwise. The mixture was allowed to warm to ambient slowly with stirring for 16 hours. The reaction mixture was then diluted with CH2Cl2 (500 mL) and washed with 1N HCl (500 mL), brine (500 ml), and dried over Na2SO4. The resultant amide product (310 g, 91%), a white solid, was obtained after solvent removal and drying under vacuum. It was then dissolved in pyridine (1.25 L) and DMAP (5 g) was added. Acetic anhydride (840 mL) was added slowly and then the reaction was heated at 90° C. for 2 hours. The cooled solution was poured into 7 L ice water and extracted with 6 L EOM. The organic layer was washed with 2N HCl (3×1 L) and 1N NaOH (1 L), dried over MgSO4 and concentrated to afford the title compound as a white solid (301 g, 93%).

Fuente