4-Methylmorpholine → [(R)-1-(3,5-Dichloro-4-fluoro-phenylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester

Temperature

20 °C

To a cooled (−20° C.) solution of (R)-2-tert-butoxycarbonylamino-propionic acid (57.2 g, 302 mmol) in anhydrous THF (582 mL) was added N-methyl-morpholine (34.9 mL, 317 mmol) at a rate to keep the internal temperature at −15° C. Isobutyl chloroformate (42.0 mL, 317 mmol) was then added over a 20 min period and the resulting mixture was stirred for 30 min. A solution of 3,5-dichloro-4-fluoro-phenylamine (54.4 g, 302 mmol) in THF (160 mL) was then added over 40 min. The reaction mixture was warmed to 20° C. and stirred for 20 h. The reaction mixture was filtered and concentrated in vacuo. To the resulting oil was added MeOH (200 mL) and the solution was concentrated to provide the title compound as a tan colored solid, m/z 295.3 [M-t-Bu]+. This material was used without further purification.

1. customat −15° C
2. stirringstirred for 20 h
3. filtrationThe reaction mixture was filtered
4. concentrationconcentrated in vacuo
5. additionTo the resulting oil was added MeOH (200 mL)
6. concentrationthe solution was concentrated

ORD record

ord-96938e9745c44d4e9167bfb93995cfb4

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481750B2