Hydrochloric Acid → {1-[2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

온도

50 °C

2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.66 g, 4.14 mmol) was dissolved in methanol (20 mL) and concentrated HCl (4 mL) was added. The mixture was stirred at 50° C. for 80 min then cooled and concentrated. The residue was treated with 2-methoxycarbonylamino-3-methyl-butyric acid (870 mg, 4.97 mmol) and HATU (2.05 g, 5.38 mmol) and brought up in DMF (20 mL). The mixture was cooled to 0° C. and DIPEA (3.60 mL, 20.7 mmol). After 100 min, the reaction mixture was diluted with ethyl acetate (250 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The resulting residue was purified by silica column chromatography (50% to 80% EtOAc/hexanes) to afford {1-[2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (1.83 g, 96% over 2 steps).

1. temperaturethen cooled
2. concentrationconcentrated
3. temperatureThe mixture was cooled to 0° C.
4. waitAfter 100 min
5. washwashed with water and brine
6. dry with materialThe organic phase was dried over magnesium sulfate
7. concentrationconcentrated
8. customThe resulting residue was purified by silica column chromatography (50% to 80% EtOAc/hexanes)

ORD 기록

ord-5ab1563ea4074a3ab2eb6843f5a4d3ed

출처 데이터셋

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08822430B2