Reacción #318898

Ecuación de reacción

tert-butyllithium

tetramethylenediamine

trifluoromethanesulfonic acid

butyllithium hexane

3-[2-bromo-1-(tert-butyldimethylsilyl)-9,10-didehydro-6-methyl-8α-ergolinyl]-1,1-diethylurea

hexamethyldisilazane

→

3-[1-(tert-butyldimetylsilyl)-9,10-didehydro-2,6-dimethyl-8α-ergolinyl]-1,1-diethylurea

Rendimiento 27.4%

Disolventes

water

toluene

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITis continued for another 15 minutes at 0° C
2. 2
   Temperaturathe batch is cooled to -90° C
3. 3
   workup.ADDITIONis added
4. 4
   ExtracciónExtraction
5. 5
   LavadoThe organic phases are washed with saturated sodium bicarbonate solution and water
6. 6
   SecadoThe combined ethyl acetate phases are dried over sodium sulfate
7. 7
   Concentraciónconcentrated
8. 8
   OtroCrystallization from methanol

Procedimiento

Under argon, 0.3 ml (1.5 mmol) of distilled hexamethyldisilazane is added to 4 ml of absolute, freshly distilled toluene, and the mixture is cooled to 0° C. Then 0.85 ml (1.4 mmol) of 15% butyllithium/hexane is added dropwise and the mixture is stirred for 15 minutes at 0° C. To this mixture is added 531 mg (1 mmol) of 3-[2-bromo-1-(tert-butyldimethylsilyl)-9,10-didehydro-6-methyl-8α-ergolinyl]-1,1-diethylurea in 50 ml of absolute, freshly distilled toluene and agitation is continued for another 15 minutes at 0° C. After adding 1 ml of distilled tetramethylenediamine, the batch is cooled to -90° C. At this temperature, 5 ml (7 mmol) of 1.4M tert-butyllithium is added and the mixture is agitated for 2 minutes before 0.6 ml (5.4 mmol) of the methyl ester of trifluoromethanesulfonic acid is added thereto. After 11/2 hours of agitation at -70° C., water is added to work up the reaction mixture. Extraction is performed with ethyl acetate. The organic phases are washed with saturated sodium bicarbonate solution and water. The combined ethyl acetate phases are dried over sodium sulfate and concentrated. Crystallization from methanol produces 128 mg of 3-[1-(tert-butyldimetylsilyl)-9,10-didehydro-2,6-dimethyl-8α-ergolinyl]-1,1-diethylurea (27% yield).

Fuente