反应 #166741

反应方程式

LHMDS

THF

1-(bromomethyl)-4-chlorobenzene

THF

tert-Butyl 2-oxopyrrolidine-1-carboxylate

LHMDS

THF

→

4-(tert-butoxycarbonylamino)-2-(4-chlorobenzyl)butanoic acid

收率 9.4%

反应条件

后处理

1. 1
   workup.STIRRINGto stir at −78° C. for 1 hour
2. 2
   其他The mixture was quenched with the addition of a 3M LiOH solution (90 mL)
3. 3
   workup.STIRRINGstirred for 48 hours at room temperature
4. 4
   workup.ADDITIONThe reaction was then diluted with water
5. 5
   洗涤washed with ethyl acetate
6. 6
   萃取extracted several times with ethyl acetate
7. 7
   洗涤The combined organic fractions were washed with water
8. 8
   干燥dried over MgSO4
9. 9
   过滤filtered
10. 10
    浓缩concentrated
11. 11
    其他to give the crude product
12. 12
    其他The crude product was purified by column chromatography (60:40 hexanes:ethyl acetate)

实验过程

LHMDS (28.3 mL, 28.3 mmol) was diluted into THF (90 mL) and cooled to −78° C. tert-Butyl 2-oxopyrrolidine-1-carboxylate (5.00 g, 27.0 mmol) was dissolved into THF (35 mL) and added to the LHMDS over a 5 minute period at −78° C. The reaction was allowed to stir for 45 minutes, and then a THF (35 mL) solution of 1-(bromomethyl)-4-chlorobenzene (5.82 g, 28.3 mmol, 1.05 equiv) was added. The reaction was allowed to stir at −78° C. for 1 hour, and then warmed to room temperature over 3 hours. The mixture was quenched with the addition of a 3M LiOH solution (90 mL) and stirred for 48 hours at room temperature. The reaction was then diluted with water and washed with ethyl acetate. The aqueous layer was acidified with 3M HCl and extracted several times with ethyl acetate. The combined organic fractions were washed with water, dried over MgSO4, filtered, and concentrated to give the crude product. The crude product was purified by column chromatography (60:40 hexanes:ethyl acetate) to give 4-(tert-butoxycarbonylamino)-2-(4-chlorobenzyl)butanoic acid (0.84 g, 9.4%).

来源