تفاعل #426420

معادلة التفاعل

(S)-2-((tert-butoxycarbonyl)(methyl)amino)propanoic acid

EDC

HOAt

NMM

(9H-fluoren-9-yl)methyl ((3S,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)carbamate

→

title compound

المردود 77.2%

tert-Butyl ((S)-1-(((S)-1-((2S,4S)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

المردود 77.2%

المذيبات

water

DMF

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe reaction mixture was stirred at rt for 2 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 sat. aq. NaHCO3 solution, 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 40% EtOAc in CH2Cl2)

الإجراء التجريبي

To a solution of (S)-2-((tert-butoxycarbonyl)(methyl)amino)propanoic acid (Chem-Impex, 2.49 g, 12.3 mmol) in DMF (20 mL) at 0° C. were added EDC (2.94 g, 15.3 mmol), HOAt (2.09 g, 15.3 mmol) and NMM (2.81 mL, 25.6 mmol). The reaction mixture was stirred at ice bath temperature for 20 min, and then treated with a solution of (9H-fluoren-9-yl)methyl ((3S,5S)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)carbamate (6.45 g, 10.2 mmol) in DMF (5 mL). The reaction mixture was stirred at rt for 2 h and then cold water (200 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). The organic solution was washed with sat. aq. NaHCO3 solution, 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 40% EtOAc in CH2Cl2) provided the title compound (6.14 g, 77%) as a light tan solid. MS (ESI+) m/z 780.5 (M+H)+.

المصدر