Reacción #1097753

Ecuación de reacción

sodium hydride

ammonium chloride

ethyl 3-[((3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidin-1-yl)-2,5-difluoro-3-methylphenyl]-3-oxopropionate

N,N-dimethylformamide dimethylacetal

cyclopropylamine

→

title compound

Rendimiento 34.5%

Ethyl 7-[(3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate

Rendimiento 34.5%

Disolventes

benzene

Condiciones de reacción

Tratamiento posterior

1. 1
   ConcentraciónThe reaction mixture was concentrated under reduced pressure
2. 2
   workup.DISSOLUTIONThe obtained residue was dissolved in dichloromethane (20 mL)
3. 3
   Temperaturaunder cooling with ice
4. 4
   ConcentraciónThe reaction mixture was concentrated under reduced pressure
5. 5
   workup.DISSOLUTIONThe obtained residue was dissolved in 1,4-dioxane (30 mL)
6. 6
   workup.STIRRINGby stirring for 2 hours
7. 7
   ExtracciónThe resultant mixture was extracted with ethyl acetate (200 mL×2)
8. 8
   Lavadowashed by saturated brine (100 mL)
9. 9
   Secadodried over anhydrous sodium sulfate
10. 10
    FiltraciónAfter filtration
11. 11
    Concentraciónthe filtrate was concentrated under reduced pressure
12. 12
    OtroThe obtained residue was purified through silica gel column chromatography (chloroform:methanol=25:1)

Procedimiento

A solution of ethyl 3-[((3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidin-1-yl)-2,5-difluoro-3-methylphenyl]-3-oxopropionate (2.58 g, 5.86 mmol) and N,N-dimethylformamide dimethylacetal (3.99 mL, 30.0 mmol) in benzene (40 mL) was refluxed for 4 hours. The temperature of the reaction mixture was cooled to room temperature. The reaction mixture was concentrated under reduced pressure. The obtained residue was dissolved in dichloromethane (20 mL), and cyclopropylamine (693 μL, 10.0 mmol) was added dropwise to the solution under cooling with ice, followed by stirring at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure. The obtained residue was dissolved in 1,4-dioxane (30 mL), and 55% oily sodium hydride (436 mg, 10.0 mmol) was added to the solution at room temperature, followed by stirring for 2 hours. Subsequently, the resultant mixture was poured to an ice-cooling saturated aqueous ammonium chloride solution. The resultant mixture was extracted with ethyl acetate (200 mL×2), washed by saturated brine (100 mL), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was purified through silica gel column chromatography (chloroform:methanol=25:1), to thereby yield the title compound (957 mg, 33.4%).

Fuente