Реакция #1563926

Уравнение реакции

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

2-(4-fluorophenoxy)acetaldehyde

acetic acid

sodium triacetoxyborohydride

→

title compound

Выход 70.4%

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

Выход 70.4%

Растворители

DCE

Условия реакции

Обработка

1. 1
   ДругоеQuench
2. 2
   Другоеthe reaction with saturated aqueous NaHCO3 (25 mL)
3. 3
   Экстракцияextract the aqueous layer with EtOAc (2×25 mL)
4. 4
   ПромывкаWash the combined organic layers with saturated aqueous NaCl (25 mL)
5. 5
   Сушкаdry the organic phase over MgSO4
6. 6
   Фильтрацияfilter
7. 7
   Концентрированиеconcentrate under reduced pressure
8. 8
   Промывкаeluting with a gradient of 0% to 100% EtOAc/hexanes
9. 9
   КонцентрированиеConcentrate the fractions
10. 10
    workup.ADDITIONcontaining the desired product under reduced pressure

Методика

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)+.

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