反应详情

温度

-65 °C

Potassium tert-butoxide 1.7M in THF (602.08 mL, 1023.5 mmol) was added dropwise over a period of 2.5 h to a stirred solution of 3-(benzhydrylidene-amino)-1-methyl-pyrrolidin-2-one (259 g, 930.48 mmol) (which may be prepared as described in Description 101) and 80% solution of propargyl bromide in toluene (124.37 mL, 1116.6 mmol) in 3 A-molecular-sieve-dried reagent grade THF (1900 mL) at −65° C. under nitrogen, in a 5 L flask equipped with an overhead stirrer. After the addition was complete, the mixture was stirred at −65° C. for a further 1 h. The cooling bath was removed and a saturated solution of NaHCO3 (140 ml) was added over 1 minute (at −60° C.). After a further 5 mins more sat NaHCO3 solution (1.4 L) was added followed by Et2O (1.4 L). The mixture was stirred for 1 h then transferred to a separating funnel and water (1.4 L) was added to dissolve all solids. The layers were separated and the aqueous further extracted with Et2O (2×1 L). The combined organic extracts were re-washed with sat. brine (700 ml), diluted with water (700 ml). The organic layer was dried (MgSO4) and evaporated to a volume of approx. 500-600 ml whereupon crystallization started to occur. To this stirred mixture was then added iso-hexane (1.6 L). After standing for 15 mins the cream solid was filtered under suction and washed with iso-hexane (500 ml) and dried at 50° C. under vacuum for 5 h. This afforded 3-(benzhydrylidene-amino)-1-methyl-3-prop-2-ynyl-pyrrolidin-2-one (D102) (274 g, 93%). This was pure by NMR but contains some additional water;

1. customequipped with an overhead stirrer
2. additionAfter the addition
3. customThe cooling bath was removed
4. additiona saturated solution of NaHCO3 (140 ml) was added over 1 minute (at −60° C.)
5. waitAfter a further 5 mins more sat
6. additionNaHCO3 solution (1.4 L) was added
7. stirringThe mixture was stirred for 1 h
8. customthen transferred to a separating funnel
9. additionwater (1.4 L) was added
10. dissolutionto dissolve all solids
11. customThe layers were separated
12. extractionthe aqueous further extracted with Et2O (2×1 L)
13. washThe combined organic extracts were re-washed with sat. brine (700 ml)
14. additiondiluted with water (700 ml)
15. dry with materialThe organic layer was dried (MgSO4)
16. customevaporated to a volume of approx. 500-600 ml whereupon crystallization
17. waitAfter standing for 15 mins
18. filtrationthe cream solid was filtered under suction
19. washwashed with iso-hexane (500 ml)
20. customdried at 50° C. under vacuum for 5 h