反应 #2358543

反应方程式

(S)-3-((R)-1-hydroxy-2-methylpropyl)pyrrolidine-1-carboxylic acid t-butyl ester

p-chlorophenol

Diisopropyl azodicarboxylate

triphenylphosphine

→

(S)-3-[(S)-1-(4-chlorophenoxy)-2-methylpropyl]pyrrolidine-1-carboxylic acid t-butyl ester

收率 10.8%

溶剂

—

Hexanes

—

hexanes

2-methyl-tetrahydrofuran

反应条件

后处理

1. 1
   其他the vessel purged with nitrogen
2. 2
   workup.STIRRINGthe resulting mixture was stirred at room temperature for 30 minutes
3. 3
   其他The phases were separated
4. 4
   洗涤the organic layer was washed with 1.0 M NaOH in water (600 mL)
5. 5
   洗涤washed with diluted saturated aqueous NaCl (20 mL)
6. 6
   干燥dried over Na2SO4
7. 7
   其他to yield the crude BOC-
8. 8
   workup.STIRRINGthe resulting mixture was stirred for 30 minutes
9. 9
   过滤Solids were filtered off
10. 10
    其他to yield the crude BOC-
11. 11
    其他was then purified by silica gel chromatography (0-10-20% EtOAc in hexanes)

实验过程

(S)-3-((R)-1-hydroxy-2-methylpropyl)pyrrolidine-1-carboxylic acid t-butyl ester (35.0 g, 144 mmol, 1.0 eq.), triphenylphosphine (41.5 g, 158 mmol, 1.1 eq.), p-chlorophenol (37.0 g, 288 mmol, 2.0 eq.) and 2-methyl-tetrahydrofuran (300 mL) were combined and the vessel purged with nitrogen. Diisopropyl azodicarboxylate (31.2 mL, 1.1 eq.) was added slowly at room temperature over 2 hours. The mixture was then stirred at room temperature overnight. Hexanes (600 mL) were added and the resulting mixture was stirred at room temperature for 30 minutes. The phases were separated and the organic layer was washed with 1.0 M NaOH in water (600 mL), washed with diluted saturated aqueous NaCl (20 mL), then dried over Na2SO4 to yield the crude BOC-protected intermediate. Additional hexanes (50 mL) were added and the resulting mixture was stirred for 30 minutes. Solids were filtered off to yield the crude BOC-protected intermediate as a thick oil, which was then purified by silica gel chromatography (0-10-20% EtOAc in hexanes) to yield (S)-3-[(S)-1-(4-chlorophenoxy)-2-methylpropyl]pyrrolidine-1-carboxylic acid t-butyl ester (5.5 g).

来源