Реакция #489722

Уравнение реакции

sodium hydride

1-benzyloxy-7-chloro-6-fluoro-isoquinoline

1-Benzyloxy-7-chloro-6-fluoro-isoquinoline

3-amino-cyclobutanol

3-Amino-cyclobutanol

→

title compound ( 51 )

Выход 30.5%

3-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-cyclobutylamine

Выход 30.5%

Растворители

dimethyl acetamide

dimethyl acetamide

dimethyl acetamide

Условия реакции

Обработка

1. 1
   workup.ADDITIONwas added
2. 2
   Другоеwas continued first at room temperature
3. 3
   ДругоеThe reaction was quenched by addition of water
4. 4
   Экстракцияthe reaction mixture was extracted three times
5. 5
   workup.ADDITIONwith a mixture of dichloromethane and 2-propanol (3:1)
6. 6
   ДругоеThe combined organic layers were evaporated
7. 7
   workup.ADDITIONwater was added
8. 8
   Другоеto remove remainders of dimethyl acetamide
9. 9
   ДругоеThe obtained crude product
10. 10
    Другоеwas purified by silica gel chromatography

Методика

To a suspension of 459 mg (11.5 mmol) of sodium hydride (60%) in 16 mL of dimethyl acetamide was added a solution of 333 mg (3.82 mmol) of 3-amino-cyclobutanol (50) in 8 ml of dimethyl acetamide. After stirring for 60 min at room temperature a solution of 1.00 g (3.48 mmol) of 1-benzyloxy-7-chloro-6-fluoro-isoquinoline (11) in 16 ml of dimethyl acetamide was added and stirring was continued first at room temperature, then for 2 h at 50° C. until the reaction went to completion. The reaction was quenched by addition of water and the reaction mixture was extracted three times with a mixture of dichloromethane and 2-propanol (3:1). The combined organic layers were evaporated, water was added and the crude product was subjected to lyophilization to remove remainders of dimethyl acetamide. The obtained crude product was purified by silica gel chromatography to yield 377 mg of the title compound (51) as a mixture of diastereoisomers. Rt=0.85 min (Method H). Detected mass: 355.1 (M+H+).

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