Reacción #345150

Ecuación de reacción

lithium bis(trimethylsilyl)amide

(4-carboxybutyl)triphenylphosphonium bromide

Water

(2S,4R)-1-t-butoxycarbonyl-4-(4-chlorophenylsulfonylamino)-2-formylpyrrolidine

→

(2S,4R)-1-t-butoxycarbonyl-2-[(Z)-5-carboxy-1-pentenyl]-4-(4-chlorophenylsulfonylamino)pyrrolidine

Rendimiento 63.0%

Disolventes

tetrahydrofuran

ethyl acetate

tetrahydrofuran

hexamethylphosphoramide

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter the solution was cooled to -25° C.
2. 2
   workup.STIRRINGthe solution was stirred at -20° C.~-25° C. for 30 minutes
3. 3
   Otrothe aqueous phase was separated
4. 4
   Extracciónextracted with ethyl acetate (200 ml)
5. 5
   LavadoThe organic layer was washed two times with water
6. 6
   Secadowith brine and dried over magnesium sulfate
7. 7
   OtroThe solvent was evaporated in vacuo
8. 8
   Otrothe residue was chromatographed on a silica gel (150 g) column with a mixture of chloroform and methanol (30:1) as an eluent

Procedimiento

To a suspension of (4-carboxybutyl)triphenylphosphonium bromide (13.3 g) in a mixture of tetrahydrofuran (80 ml) and hexamethylphosphoramide (20 ml) was added a solution (60 ml, 1M solution) of lithium bis(trimethylsilyl)amide in tetrahydrofuran at 0° C. and the solution was stirred at room temperature for 1 hour. After the solution was cooled to -25° C., a solution of (2S,4R)-1-t-butoxycarbonyl-4-(4-chlorophenylsulfonylamino)-2-formylpyrrolidine (3.89 g) in tetrahydrofuran (20 ml) was added dropwise thereto and the solution was stirred at -20° C.~-25° C. for 30 minutes. Water (100 ml) and ethyl acetate (100 ml) were added to the solution and the aqueous phase was separated. The aqueous solution was adjusted to pH2 with 1N hydrochloric acid and extracted with ethyl acetate (200 ml). The organic layer was washed two times with water and then with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was chromatographed on a silica gel (150 g) column with a mixture of chloroform and methanol (30:1) as an eluent to give (2S,4R)-1-t-butoxycarbonyl-2-[(Z)-5-carboxy-1-pentenyl]-4-(4-chlorophenylsulfonylamino)pyrrolidine (2.98 g) as a colorless oil.

Fuente