Реакция #2146763

Уравнение реакции

sodium hydride

benzyl alcohol

benzyl alcohol

sodium hydride

sodium hydride

1,7-dichloro-6-fluoro-isoquinoline

1,7-Di-chloro-6-fluoro-isoquinoline

4-hydroxy-piperidine-1-carboxylic acid tert-butyl-ester

→

4-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl-ester

Растворители

dimethyl acetamide

dimethyl acetamide

Условия реакции

Обработка

1. 1
   workup.STIRRINGthe mixture was stirred at room temperature for 1 h
2. 2
   workup.ADDITIONwere added
3. 3
   workup.STIRRINGstirring
4. 4
   Другоеwas continued at room temperature
5. 5
   workup.ADDITIONwere added twice, after 2 h
6. 6
   Другоеthe solvent was evaporated
7. 7
   Промывкаwashed twice with H2O
8. 8
   Сушкаdried with MgSO4
9. 9
   Другоеevaporated
10. 10
    ДругоеFinal purification

Методика

289.8 mg (1.44 mmol) of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl-ester were dissolved in 10 ml of dimethyl acetamide and 57.6 mg (1.44 mmol) of sodium hydride (60%) were added. The reaction mixture was stirred at room temperature. After 30 minutes a solution of 310 mg (1.44 mmol) of 1,7-dichloro-6-fluoro-isoquinoline (5) in 3 ml of dimethyl acetamide was added and the mixture was stirred at room temperature for 1 h to complete conversion. Then 155.7 mg (1.44 mmol) of benzyl alcohol followed by 57.6 mg (1.44 mmol) of sodium hydride (60%) were added and stirring was continued at room temperature. To reach complete conversion, 0.5 equivalents of benzyl alcohol and sodium hydride were added twice, after 2 h and standing overnight. For working up, the solvent was evaporated, the residue was taken up in dichloromethane, washed twice with H2O, dried with MgSO4 and evaporated. Final purification was accomplished by preparative HPLC.

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