反应详情

To a solution of 2-methyl-2-(1-pyrrolidinyl)propanenitrile D4 (40 g; 289.85 mmol) in dry THF (0.8 L) under nitrogen, cooled at −78° C., was added dropwise a solution of phenyl lithium in dibutyl ether over 40 minutes (305.1 mL of a 1.9M solution; 579.70 mmol). After 2 h the reaction was allowed to reach room temperature and then stirred overnight at this temperature. The mixture was quenched at 0° C. with a saturated solution of NaHCO3 (0.8 L) and stirred for 15 minutes and diluted with water (ca. 0.6 L). The phases were separated and the aqueous back extracted with diethylether (2×1 L). The collected organics were dried over Na2SO4 and evaporated in vacuo to get 90 g of crude material as a yellow oil that was dissolved in methanol (1 L) at 0° C. and treated portionwise with sodium borohydride (21.93 g; 579.70 mmol). After 1 hour at 0° C. and then overnight at room temperature the mixture was cooled and quenched with water (ca. 0.5 L). Methanol was evaporated in vacuo and the aqueous phase, diluted with water (200 mL), was extracted with DCM (3×800 mL). The collected organics were dried over Na2SO4 and evaporated in vacuo to get the title product (51 g) as a yellow solid, used in step 2 without further purification.

1. customto reach room temperature
2. customThe mixture was quenched at 0° C. with a saturated solution of NaHCO3 (0.8 L)
3. stirringstirred for 15 minutes
4. additiondiluted with water (ca. 0.6 L)
5. customThe phases were separated
6. extractionthe aqueous back extracted with diethylether (2×1 L)
7. dry with materialThe collected organics were dried over Na2SO4
8. customevaporated in vacuo
9. customto get 90 g of crude material as a yellow oil that
10. waitAfter 1 hour at 0° C.
11. customquenched with water (ca. 0.5 L)
12. customMethanol was evaporated in vacuo
13. additionthe aqueous phase, diluted with water (200 mL)
14. extractionwas extracted with DCM (3×800 mL)
15. dry with materialThe collected organics were dried over Na2SO4
16. customevaporated in vacuo