Реакция #426418

Уравнение реакции

(2S,4S)-Boc-gamma-(Fmoc-amino)-proline

EDC

HOAt

NMM

(R)-1,2,3,4-tetrahydronaphthalen-1-amine

→

title compound

Выход 87.0%

(2S,4S)-tert-Butyl 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidine-1-carboxylate

Выход 87.0%

Растворители

water

DMF

DMF

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe reaction mixture was stirred at rt for 1 h
2. 2
   ДругоеThe solid that formed
3. 3
   Фильтрацияwas collected by filtration
4. 4
   Промывкаwashed with cold water (100 mL)
5. 5
   workup.DISSOLUTIONThe solid was dissolved in CH2Cl2 (200 mL)
6. 6
   Промывкаthe organic solution was washed with 5% aq. citric acid solution and brine
7. 7
   Сушкаdried over MgSO4
8. 8
   Фильтрацияfiltered
9. 9
   КонцентрированиеThe filtrate was concentrated in vacuo
10. 10
    workup.DISSOLUTIONThe residue was dissolved in CH2Cl2
11. 11
    Другоеpurified by flash column chromatography (gradient elution from 10 to 30% EtOAc in CH2Cl2)

Методика

To a solution of (2S,4S)-Boc-gamma-(Fmoc-amino)-proline (Chem-Impex, 6.00 g, 13.3 mmol) in DMF (20 mL) at 0° C. were added EDC (3.05 g, 15.9 mmol), HOAt (2.17 g, 15.9 mmol) and NMM (4.38 mL, 39.8 mmol). The reaction mixture was stirred at ice bath temperature for 20 min then treated with a solution of (R)-1,2,3,4-tetrahydronaphthalen-1-amine (Alfa Aesar, 2.15 g, 14.6 mmol) in DMF (2 mL). The reaction mixture was stirred at rt for 1 h and cold water (100 mL) was added to the reaction mixture. The solid that formed was collected by filtration and washed with cold water (100 mL). The solid was dissolved in CH2Cl2 (200 mL) and the organic solution was washed with 5% aq. citric acid solution and brine, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo. The residue was dissolved in CH2Cl2 and purified by flash column chromatography (gradient elution from 10 to 30% EtOAc in CH2Cl2) provided the title compound (6.70 g, 87%) as a light tan solid. 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J=7.5 Hz, 2H), 7.67 (d, J=7.3 Hz, 2H), 7.42 (td, J=7.2, 4.0 Hz, 2H), 7.37-7.03 (m, 6H), 5.22 (br. s., 1H), 4.57-4.23 (m, 5H), 3.68-3.49 (m, 2H), 2.91-2.74 (m, 2H), 2.52 (d, J=13.4 Hz, 1H), 2.35-2.21 (m, 1H), 2.14 (d, J=5.1 Hz, 1H), 1.97-1.80 (m, 3H), 1.44 (s, 9H); MS (ESI+) m/z 582.2 (M+H)+.

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