反应 #164158

反应方程式

HCl dioxane

2-(tert-butoxycarbonylamino)-2-phenylacetic acid

HOBt

DCC

3(R)-quinuclidinol

di hydrochloride

(R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-phenylacetate

→

(R)-quinuclidin-3-yl 2-amino-2-phenylacetate di-hydrochloride

收率 97.0%

溶剂

THF

DCM

反应条件

后处理

1. 1
   其他The solvent is removed under reduced pressure
2. 2
   洗涤washed twice with 2M K2CO3
3. 3
   干燥The organic phase is dried over Na2SO4
4. 4
   过滤filtered
5. 5
   其他evaporated to dryness
6. 6
   其他The compound is triturated with hexane
7. 7
   其他to give
8. 8
   workup.STIRRINGThe reaction is stirred at room temperature for 1 hour (LC-MS monitoring: complete conversion)
9. 9
   其他solvent is separated
10. 10
    其他The gummy solid is triturated with hexane
11. 11
    其他to give C25

实验过程

A mixture of 2-(tert-butoxycarbonylamino)-2-phenylacetic acid (0.90 g, 4.18 mmol), HOBt (0.68 g, 12.5 mmol), DCC (1.29 g, 6.27 mmol) and 3(R)-quinuclidinol (1.59 g, 12.5 mmol) in dry THF (50 mL) is stirred at room temperature for 16 hours (LC-MS monitoring: complete conversion). The solvent is removed under reduced pressure, the residue is taken up with EtOAc and washed twice with 2M K2CO3. The organic phase is dried over Na2SO4, filtered and evaporated to dryness. The compound is triturated with hexane to give (R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-phenylacetate as a white solid (1.46 g; 97% yield, mixture of diastereoisomers). This compound is dissolved in DCM (50 mL) and 4N HCl dioxane (5 mL) is added. The reaction is stirred at room temperature for 1 hour (LC-MS monitoring: complete conversion) and then solvent is separated. The gummy solid is triturated with hexane to give C25 as a white solid (1.26 g, 94% yield, di hydrochloride, mixture of diastereoisomers).

来源