반응 #1563926

반응 방정식

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

2-(4-fluorophenoxy)acetaldehyde

acetic acid

sodium triacetoxyborohydride

→

title compound

수율 70.4%

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

수율 70.4%

용매

DCE

반응 조건

후처리

1. 1
   기타Quench
2. 2
   기타the reaction with saturated aqueous NaHCO3 (25 mL)
3. 3
   추출extract the aqueous layer with EtOAc (2×25 mL)
4. 4
   세척Wash the combined organic layers with saturated aqueous NaCl (25 mL)
5. 5
   건조dry the organic phase over MgSO4
6. 6
   여과filter
7. 7
   농축concentrate under reduced pressure
8. 8
   세척eluting with a gradient of 0% to 100% EtOAc/hexanes
9. 9
   농축Concentrate the fractions
10. 10
    workup.ADDITIONcontaining the desired product under reduced pressure

실험 절차

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)+.

출처