反応 #164158

反応方程式

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

収率 97.0%

溶媒

THF

DCM

反応条件

後処理

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

実験手順

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).

出典