反应详情

温度

50 °C

n-Butyllithium (2.6M in hexane, 295.5 mL, 0.77 mol) was added dropwise at 0°-3° C., with stirring, to a solution of di(isopropyl)amine (109.3 mL, 78.9 g, 0.78 mol) in tetrahydrofuran (freshly distilled, 200 mL). The resulting solution was transferred to an addition funnel and added dropwise at room temperature to a stirred solution of methyl N-(2-chloroethyl)-3-methoxycarbonyl-2-pyrroleacetate (150.0 g, 0.58 mol) in tetrahydrofuran (dry, 750 mL). The addition took 4 hours, and the temperature was maintained in the range of 23°-27° C. The resulting solution was stirred for 16 hours, then diluted with water (500 mL) over 10 minutes with slight heat evolution. The solvents were stripped by atmospheric distillation to a pot temperature of 75° C. The pot solution was cooled to 50° C. and sodium hydroxide (53.0 g, 1.33 mol) added; then methanol was removed by atmospheric distillation to a pot temperature of 95° C.; with a total of 1370 mL of solvents collected. The pot solution was cooled to -3°-0° C. and acidified with hydrochloric acid (12M, 180 mL, 216 mmol), resulting in a temperature rise to 18° C. The resulting mixture was cooled to -3°-0° C., aged for 30 minutes at that temperature, and filtered, and the precipitate washed with ice-cold water (300 mL) and dried, to give 107.8 g of crude 2,3-dihydro-1H-pyrrolo[1,2-a]pyrrole-1,7-dicarboxylic acid. Assay of the crude material indicated that it contained 96.6% 2,3-dihydro-1H-pyrrolo-[1,2-a]pyrrole-1,7-dicarboxylic acid.

1. distillationfreshly distilled
2. customThe resulting solution was transferred to an addition funnel
3. additionThe addition
4. temperaturethe temperature was maintained in the range of 23°-27° C
5. distillationThe solvents were stripped by atmospheric distillation to a pot temperature of 75° C
6. customthen methanol was removed by atmospheric distillation to a pot temperature of 95° C.
7. customwith a total of 1370 mL of solvents collected
8. temperatureThe pot solution was cooled to -3°-0° C.
9. customresulting in a temperature rise to 18° C
10. temperatureThe resulting mixture was cooled to -3°-0° C.
11. waitaged for 30 minutes at that temperature
12. filtrationfiltered
13. washthe precipitate washed with ice-cold water (300 mL)
14. customdried