反应 #51500

反应方程式

n-butyllithium

LDA

ICH2Cl

(2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid methyl ester

→

title compound

tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate

溶剂

THF

反应条件

后处理

1. 1
   温度The mixture is cooled to −78°
2. 2
   温度maintaining an internal temperature below −60°
3. 3
   workup.ADDITIONOnce the addition
4. 4
   workup.ADDITIONis added dropwise
5. 5
   温度maintaining an internal temperature below about −60°
6. 6
   其他then quenched into 0° hydrochloric acid (IN)
7. 7
   workup.ADDITIONEthyl acetate is added
8. 8
   其他the phases are separated
9. 9
   萃取the aqueous phase is extracted with ethyl acetate
10. 10
    洗涤The combined organic phases are washed with saturated sodium bicarbonate
11. 11
    干燥dried over sodium sulfate
12. 12
    过滤filtered
13. 13
    浓缩concentrated under reduced pressure

实验过程

ICH2Cl (3.54 g, 1.46 mL, 19.82 mmol, 1.25 equivalent) and THF (5 mL) are added to (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid methyl ester (II, EXAMPLE 1, 5 g, 15.86 mmol, 1 equivalent). The mixture is cooled to −78° and LDA (22.3 mL, 44.60 mmol, 2.25 equivalents, 2.0M) is added dropwise maintaining an internal temperature below −60°. Once the addition is complete, the contents are stirred for 30 min at −78° at which time n-butyllithium (15.3 mL, 19.82 mmol, 1.25 equivalents; 1.3M in hexanes) is added dropwise maintaining an internal temperature below about −60°. The reaction is stirred for 30 min then quenched into 0° hydrochloric acid (IN). Ethyl acetate is added and the phases are separated and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound, NMR (DMSO-d6) δ 7.47, 7.06-7.14, 4.78, 4.49, 3.20, 2.82 and 1.40; CMR (DMSO-d6) δ 200.87, 163.74, 161.20, 142.74, 112.80, 102.13, 79.04, 58.97, 47.72, 34.95 and 28.30.

来源