تفاعل #66732

معادلة التفاعل

sodium hydride

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

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

4-amino-adamantan-1-ol

→

title compound

المردود 31.2%

5-(1-Benzyloxy-7-chloro-isoquinolin-6-yloxy)-adamantan-2-ylamine

المردود 31.2%

المذيبات

dimethyl acetamide

dimethyl acetamide

dimethyl acetamide

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGstirring
2. 2
   أخرىwas continued at room temperature until the reaction
3. 3
   أخرىThe reaction was quenched by addition of water (15 mL)
4. 4
   استخلاصthe reaction mixture was extracted twice with a mixture of dichloromethane and 2-propanol (3:1)
5. 5
   أخرىThe combined organic layers were evaporated
6. 6
   workup.ADDITIONwater was added
7. 7
   أخرىto remove remainders of dimethyl acetamide
8. 8
   أخرىThe obtained crude product
9. 9
   أخرىwas purified by flash chromatography (SiO2, 0%→30% methanol in dichloromethane)

الإجراء التجريبي

To a suspension of sodium hydride (60% in mineral oil, 417 mg, 10.4 mmol, 3 eq.) in dimethyl acetamide (7 mL) was added a solution of 4-amino-adamantan-1-ol (640 mg, 3.82 mmol, 1.1 eq.) in dimethyl acetamide (7 mL). After stirring for 60 min at room temperature, a solution of 1-benzyloxy-7-chloro-6-fluoro-isoquinoline (1, 1.0 g, 3.48 mmol) in dimethyl acetamide (7 mL) was added and stirring was continued at room temperature until the reaction went to completion. The reaction was quenched by addition of water (15 mL) and the reaction mixture was extracted twice with a mixture of dichloromethane and 2-propanol (3:1). The combined organic layers were evaporated, water was added and the mixture was subjected to lyophilization to remove remainders of dimethyl acetamide. The obtained crude product was purified by flash chromatography (SiO2, 0%→30% methanol in dichloromethane) to yield 473 mg of the title compound as diastereomeric mixture. Rt=1.35 min, 1.55 min (Method 3). Detected mass: 435.2 (M+H+).

المصدر