反応 #476379

反応方程式

Potassium t-butoxide

BOC trans-4-hydroxyproline

product

7-Bromo-1-chloro-6-methoxyisoquinoline

→

title compound

収率 70.3%

Ethyl (4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-L-prolinate hydrochloride

収率 70.3%

溶媒

DMSO

反応条件

後処理

1. 1
   workup.STIRRINGThe reaction mixture was stirred overnight
2. 2
   その他partitioned between ice-cold 10% citric acid and EtOAc
3. 3
   洗浄The organic phase was washed with water and brine
4. 4
   乾燥dried over Na2SO4
5. 5
   その他the solvent evaporated
6. 6
   workup.DISSOLUTIONThe crude product was dissolved in EtOH (100 mL)
7. 7
   温度cooled to 0° C.
8. 8
   その他HCl bubbled through until saturated
9. 9
   温度to warm to RT
10. 10
    workup.STIRRINGstirred for 24 hours
11. 11
    その他The volatiles were evaporated
12. 12
    その他the residue azeotroped with EtOH (4×)

実験手順

Potassium t-butoxide (618 mg, 5.5 mmol) was added to a stirred solution of BOC trans-4-hydroxyproline (424 mg, 1.83 mmol) in DMSO (10 mL) at RT. The reaction mixture was stirred for 30 minutes and cooled to 15° C., and the product from Step 3 (500 mg, 1.83 mmol) was added. The reaction mixture was stirred overnight and partitioned between ice-cold 10% citric acid and EtOAc. The organic phase was washed with water and brine, dried over Na2SO4, and the solvent evaporated. The crude product was dissolved in EtOH (100 mL), cooled to 0° C. and HCl bubbled through until saturated. The reaction mixture was allowed to warm to RT and stirred for 24 hours. The volatiles were evaporated and the residue azeotroped with EtOH (4×) to give the title compound as a tan solid (555 mg). LRMS ESI+ (M+H)+ 395.0.

出典