Reacción #47854

Ecuación de reacción

DMF

N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

THF

butyllithium

→

N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-formylthiophene-2-carboxamide

Disolventes

EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroIn 150 mL round-bottom flask equipped with a stir bar, under N2
2. 2
   workup.STIRRINGThe mixture was stirred at −78° C. for 0.5 hr
3. 3
   Otroquenched with saturated solution of NH4Cl
4. 4
   Temperaturato warm up to room temperature
5. 5
   OtroThe reaction
6. 6
   Otrothe layers were separated
7. 7
   Extracciónthe aqueous layer was extracted with EtOAc (3×50 ml)
8. 8
   Lavadothe combined organic solution was washed with brine, water
9. 9
   Secadodried over MgSO4
10. 10
    OtroThe organic solutions were evaporated under reduced pressure
11. 11
    Otrochromatographed through a Redi-Sep pre-packed silica gel column (40 g)
12. 12
    Lavadoeluting with a gradient of 5% to 95% MeOH in DCM

Procedimiento

In 150 mL round-bottom flask equipped with a stir bar, under N2, was added N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide (1.2 g, 3.4 mmol) followed by anhydrous THF (100 mL). The solution was cooled down to −78° C. and butyllithium, (2.2 ml, 30 mmol) was added dropwise over 5 min. The mixture was stirred at −78° C. for 0.5 hrs and was added DMF (0.780 ml, 10 mmol). The mixture was stirred at −78° C. for 0.5 hr, quenched with saturated solution of NH4Cl and then allowed to warm up to room temperature. The reaction then diluted with EtOAc (100 ml) and the layers were separated and the aqueous layer was extracted with EtOAc (3×50 ml) and the combined organic solution was washed with brine, water and dried over MgSO4. The organic solutions were evaporated under reduced pressure and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 5% to 95% MeOH in DCM to provide N-tert-butyl-5-(5-(cyclopropylcarbamoyl)-2-methylphenyl)-3-formylthiophene-2-carboxamide (1.01 g). MS (ES+): 385 (M+H)+

Fuente