4-Methylmorpholine → tert-Butyl (2R)-2-{[(2-bromophenyl)amino]carbonyl}pyrrolidine-1-carboxylate

Temperatur

0 °C

In a 500 mL flask, N-Boc-D-Proline (300 mg, 1.39 mmol) was dissolved in dichloromethane (35 mL) and cooled to 0° C. under nitrogen. N-Methylmorpholine (153 μL, 1.39 mmol) was added followed by dropwise addition of iso-butyl chloroformate (180 μL, 1.39 mmol) and the reaction mixture stirred at 0° C. for 1 h. 2-Bromoaniline (1.31 mL, 1.39 mmol) was dissolved in dichloromethane (5 mL) then added quickly to the activated acid at 0° C. The mixture was stirred overnight from 0° C. to room temperature. The reaction mixture was diluted with dichloromethane, washed with water, dried over Na2SO4 and concentrated under reduced pressure. The crude mixture was purified on column chromatography (eluent: Pentane/EtOAc, 50/50 to 0/100 then EtOAc/MeOH 80/20) to give the product (394 mg, 77%) as a yellow oil. This product was used in the next step without further purification.

1. additionthen added quickly to the activated acid at 0° C
2. stirringThe mixture was stirred overnight from 0° C. to room temperature
3. washwashed with water
4. dry with materialdried over Na2SO4
5. concentrationconcentrated under reduced pressure
6. customThe crude mixture was purified on column chromatography (eluent

ORD-Eintrag

ord-425324b66c054063972e3e28ef32dde3

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08846711B2