Reacción #166983

Ecuación de reacción

2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HCl

2-methoxycarbonylamino-3-methyl-butyric acid

HATU

DIPEA

→

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

Rendimiento 96.5%

Disolventes

DMF

ethyl acetate

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathen cooled
2. 2
   Concentraciónconcentrated
3. 3
   TemperaturaThe mixture was cooled to 0° C.
4. 4
   workup.WAITAfter 100 min
5. 5
   Lavadowashed with water and brine
6. 6
   SecadoThe organic phase was dried over magnesium sulfate
7. 7
   Concentraciónconcentrated
8. 8
   OtroThe resulting residue was purified by silica column chromatography (50% to 80% EtOAc/hexanes)

Procedimiento

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).

Fuente