Reacción #1563926

Ecuación de reacción

methyl 4-[(1S)-1-[[(2R)-piperidine-2-carbonyl]amino]ethyl]benzoate hydrochloride

2-(4-fluorophenoxy)acetaldehyde

acetic acid

sodium triacetoxyborohydride

→

title compound

Rendimiento 70.4%

methyl 4-[(1S)-1-[[(2R)-1-(2-(4-fluorophenoxy)ethyl)piperidine-2-carbonyl]amino]ethyl]benzoate

Rendimiento 70.4%

Disolventes

DCE

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroQuench
2. 2
   Otrothe reaction with saturated aqueous NaHCO3 (25 mL)
3. 3
   Extracciónextract the aqueous layer with EtOAc (2×25 mL)
4. 4
   LavadoWash the combined organic layers with saturated aqueous NaCl (25 mL)
5. 5
   Secadodry the organic phase over MgSO4
6. 6
   Filtraciónfilter
7. 7
   Concentraciónconcentrate under reduced pressure
8. 8
   Lavadoeluting with a gradient of 0% to 100% EtOAc/hexanes
9. 9
   ConcentraciónConcentrate the fractions
10. 10
    workup.ADDITIONcontaining the desired product under reduced pressure

Procedimiento

Stir a mixture of methyl 4-[(1S)-1-[[(2R)-piperidine-2-carbonyl]amino]ethyl]benzoate hydrochloride (650 mg, 1.99 mmol) and 2-(4-fluorophenoxy)acetaldehyde (337 mg, 2.19 mmol) in DCE (9.9 mL) at room temperature for 30 min. Add acetic acid (0.113 mL, 1.99 mmol) and sodium triacetoxyborohydride (590 mg, 2.78 mmol) and stir at room temperature for three days. Quench the reaction with saturated aqueous NaHCO3 (25 mL) and extract the aqueous layer with EtOAc (2×25 mL). Wash the combined organic layers with saturated aqueous NaCl (25 mL), then dry the organic phase over MgSO4, filter, and concentrate under reduced pressure. Subject the resulting oil to flash chromatography on silica gel, eluting with a gradient of 0% to 100% EtOAc/hexanes. Concentrate the fractions containing the desired product under reduced pressure to provide the title compound as a white solid (600 mg, 70% yield). Mass spectrum (m/z) 429 (M+H)+, 451 (M+Na)+.

Fuente