Chlorotrimethylsilane → HCID 57528953, Verbindung

Temperatur

25 °C

To a suspension of L-aspartic acid β-methyl ester hydrochloride (Sigma, 5.0 g, 27.23 mmol) in chilled (<5° C.) CH2Cl2 (150 mL) was added Et3N (8.33 g, 81.70 mmol) in a steady flow followed by a slow addition of Me3SiCl (6.51 g, 59.92 mmol). The mixture was warmed to 25° C. and stirred for 1 h, cooled again (<10° C.), and 3-bromo4-methylbenzoyl chloride (6.36 g, 27.23 mmol) was added dropwise. The mixture was allowed to warm to ambient temperature slowly with stirring for 16 h. The reaction mixture was then diluted with CH2Cl2 (150 mL) and washed with 1N HCl (50 mL), brine (50 mL), and dried over Na2SO4. The resultant amide product (8.9 g, 95%), a white solid, was obtained after solvent removal and drying under vacuum. It was then dissolved in pyridine (50 mL) and DMAP (0.17 g, 1.38 mmol) was added. Acetic anhydride (26 mL) was added slowly and then the reaction was heated at 90° C. for 2 h. The cooled solution was poured into 200 mL ice water and extracted with EtOAc. The organic layer was washed with 2N HCl (3×100 mL) and 1N NaOH (100 mL), dried over MgSO4, and concentrated to afford the title compound as a off white solid which was taken to the next step (Example 81).

1. additionwas added dropwise
2. temperatureto warm to ambient temperature slowly
3. stirringwith stirring for 16 h
4. washwashed with 1N HCl (50 mL), brine (50 mL)
5. dry with materialdried over Na2SO4

ORD-Eintrag

ord-1634975e72fc4da8b35bcf73b659f50e

Quelldatensatz

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07476742B2