Reacción #47278

Ecuación de reacción

water

((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol

1,4-diazabicyclo[2.2.2]octane

4-chlorobenzenesulfonyl chloride

→

4-chloro-benzenesulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester

Rendimiento 93.3%

Disolventes

ethyl acetate

heptane

heptane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe resulting mixture stirred at room temperature overnight
3. 3
   Otrothe organic layer was separated
4. 4
   Lavadowashed with water (3×600 mL)
5. 5
   ConcentraciónThe mixture was concentrated under vacuum
6. 6
   Otroto provide a yellow oil which
7. 7
   ConcentraciónThe mixture was concentrated
8. 8
   Otroto remove any remaining ethyl acetate and heptane (500 mL)
9. 9
   workup.ADDITIONwas added once more
10. 10
    Otrocrystallization
11. 11
    FiltraciónThe thick white suspension was filtered
12. 12
    Lavadowashed with heptane, and suction
13. 13
    Otrodried

Procedimiento

To a solution of ((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (60.00 g, 454.0 mmol) and 1,4-diazabicyclo[2.2.2]octane (63.67 g, 567.6 mmol) in ethyl acetate 600 mL) at 15° C. was added 4-chlorobenzenesulfonyl chloride (100.6 g, 476.7 mmol) and the resulting cloudy solution stirred for 2 h before being warmed to room temperature. The resulting solution was stirred at room temperature for 4 h before cold water (300 mL) was added and the resulting mixture stirred at room temperature overnight. The mixture was diluted with heptane (600 mL) and the organic layer was separated and washed with water (3×600 mL). The mixture was concentrated under vacuum to provide a yellow oil which was treated with heptane (200 mL). The mixture was concentrated to remove any remaining ethyl acetate and heptane (500 mL) was added once more to induce crystallization. The thick white suspension was filtered, washed with heptane, and suction dried to provide 4-chloro-benzenesulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (129.93 g, 93.3%, 98.9% pure HPLC, 99.89% e.e) as a white solid.

Fuente