تفاعل #69718

معادلة التفاعل

4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride

triethylamine

2,4-bis-benzyloxy-5-isopropenyl-benzoic acid

EDC

HOAt

→

(2,4-bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone

المردود 55.2%

المذيبات

THF

DMF

DCM

EtOAc

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe reaction was then stirred at room temperature overnight
2. 2
   غسيلwashed with water, 1N NaOH and brine
3. 3
   أخرىthe EtOAc layer was separated
4. 4
   تجفيفdried (MgSO4)
5. 5
   أخرىevaporated
6. 6
   أخرىPurification by flash column chromatography
7. 7
   غسيلon SiO2, gradient elution from 0% to 5% 2M methanolic ammonia/DCM

الإجراء التجريبي

A solution of 2,4-bis-benzyloxy-5-isopropenyl-benzoic acid (145 mg; 1.2 equiv.) in DCM (5 ml) was treated with EDC (80 mg; 1.3 equiv.) and HOAt (66 mg; 1.5 equiv.) then stirred at room temperature for 30 minutes. This solution was then added to a mixture of 4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride (112 mg; 0.32 mmol) and triethylamine (90 μl; 2 equiv.) in THF (5 ml) and DMF (2 ml), the reaction was then stirred at room temperature overnight. The reaction mixture was diluted with EtOAc, washed with water, 1N NaOH and brine, the EtOAc layer was separated, dried (MgSO4) and evaporated. Purification by flash column chromatography on SiO2, gradient elution from 0% to 5% 2M methanolic ammonia/DCM gave 104 mg of (2,4-bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-hydroxy-1-methyl-piperidin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone as a yellow glass.

المصدر