تفاعل #426418

معادلة التفاعل

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

EDC

HOAt

NMM

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

→

title compound

المردود 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

المردود 87.0%

المذيبات

water

DMF

DMF

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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)+.

المصدر