Reaktion #612319

Reaktionsgleichung

Trifluoroacetic acid

1,1-dimethylethyl (4-[4-(1-benzofuran-5-yl)phenyl]-3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetate

→

title compound

Ausbeute 56.0%

(4-[4-(1-benzofuran-5-yl)phenyl]-3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetic acid

Ausbeute 56.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe reaction was concentrated to dryness
2. 2
   Sonstigethe residue was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 10-75% acetonitrile w/0.1% TFA/water w/0.1% TFA)
3. 3
   workup.ADDITIONThe product fractions were neutralized with the addition of saturated aq sodium bicarbonate
4. 4
   Extraktionextracted with dichloromethane
5. 5
   TrocknenThe organic layer was dried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo

Vorschrift

To a solution of 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (50 mg, 0.117 mmol) in N,N-dimethylformamide (1 mL) in a 5 mL microwaveable vial was added potassium carbonate (80 mg, 0.58 mmol, 5 eq) and tert-butylchloroacetate (21 mg, 0.14 mmol, 1.2 eq). The vial was capped, purged with nitrogen gas, and stirred for 16 h at 80° C. Analysis by LC/MS displayed the reaction was complete. The reaction mixture was cooled to room temperature and then poured into a mixture of dichloromethane and water. The organic layer was separated. The aqueous layer was washed with dichloromethane. The organic extractions were combined and washed 3× with a dilute brine solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude intermediate ester (MS(ES)+ m/e 487.3 [M+H]+). In a 50 mL round bottom flask, the crude 1,1-dimethylethyl (4-[4-(1-benzofuran-5-yl)phenyl]-3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetate was dissolved in 9 mL dichloromethane. Trifluoroacetic acid (1 mL, 12.98 mmol) was added to the solution, which was allowed to stir at room temperature for 16 h under a nitrogen bubbler. Analysis by LC/MS displayed the reaction complete. The reaction was concentrated to dryness and the residue was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 10-75% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound (32 mg, 56%). MS(ES)+ m/e 487.3 [M+H]+.

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