Reacción #317892

Ecuación de reacción

sodium hydride

(S)-(+)-2-pyrrolidinemethanol

3-chlorothiophene-2-carboxylic acid

1,1′-carbonyldiimidazole

→

title compound

Rendimiento 11.3%

(S)-2,3,10,10a-tetrahydro-1H,5H-pyrrolo[2,1-c]thieno[2,3-f][1,4]oxazepine-5-one

Rendimiento 11.3%

Disolventes

water

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas carefully added
2. 2
   Temperaturathe mixture was heated slowly to 150° C. with the progress of the reaction
3. 3
   Extracciónextracted with ethyl acetate
4. 4
   Lavadothe organic layer washed with water
5. 5
   Secadothen dried (Na2SO4)
6. 6
   Otroevaporated
7. 7
   Otroto give the crude product
8. 8
   OtroPurification by flash chromatography
9. 9
   Lavadoeluting with 0-10% (v/v) methanol in dichloromethane
10. 10
    Otrofollowed by crystallisation from ethyl acetate-petroleum ether (40-60)

Procedimiento

To a solution of 3-chlorothiophene-2-carboxylic acid (0.5 g; 6.325 mmol) in dimethylformamide (5 ml) was added 1,1′-carbonyldiimidazole (1.07 g; 6.64 mmol) and the solution stirred at room temperature for 1 h, followed by the addition of (S)-(+)-2-pyrrolidinemethanol (0.655 ml; 6.64 mmol). The reaction was stirred at room temperature overnight whereupon 60% sodium hydride in mineral oil (0.507 g; 12.7 mmol) was carefully added and the mixture was heated slowly to 150° C. with the progress of the reaction being monitored by thin layer chromatography. The reaction was cautiously diluted with water and extracted with ethyl acetate and the organic layer washed with water then dried (Na2SO4) and evaporated to give the crude product. Purification by flash chromatography eluting with 0-10% (v/v) methanol in dichloromethane followed by crystallisation from ethyl acetate-petroleum ether (40-60) afforded the title compound (0.15 g). M.p.: 167-167.5° C.; EIMS: m/z=222.2 [M+H]+

Fuente