تفاعل #44706

معادلة التفاعل

guanidinium carbonate

1-benzyl piperidine-1,3-dicarboxylate

(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride

→

Benzyl 3-(2-amino-6-hydroxypyrimidin-4-yl)piperidine-1-carboxylate

المذيبات

dichloromethane

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   workup.WAITat room temperature for 18 hours
2. 2
   غسيلwashed successively with water (20 ml), 1N hydrochloric acid (30 ml), saturated aqueous sodium bicarbonate solution (30 ml) and saturated aqueous sodium chloride solution
3. 3
   تجفيفThe organic phase is dried over anhydrous magnesium sulfate
4. 4
   تركيزThe solution is concentrated under reduced pressure
5. 5
   workup.DISSOLUTIONThe residue (1.2 g) is dissolved in 30 ml of ethanol
6. 6
   workup.ADDITION0.13 ml (0.61 mmol) of 37% strength hydrochloric acid is added
7. 7
   workup.STIRRINGthe mixture is stirred
8. 8
   درجة الحرارةunder reflux for one hour
9. 9
   درجة الحرارةAfter cooling
10. 10
    workup.STIRRINGthe reaction mixture is stirred
11. 11
    درجة الحرارةat reflux (oil bath temperature 93° C.) for 18 hours
12. 12
    تركيزThe solution is concentrated
13. 13
    أخرىThe crude product is purified on a silica gel column

الإجراء التجريبي

2 g (7.59 mmol) of 1-benzyl piperidine-1,3-dicarboxylate, 1.31 g (9.11 mmol) of 2,2-dimethyl-1,3-dioxolane-4,6-dione and 1.85 g (15.19 mmol) of 4-dimethylamino-pyridine are initially charged in 12 ml of dichloromethane, and the mixture is cooled to 0° C. 1.60 g (8.35 mmol) of (3-dimethylaminopropyl)ethylcarbodiimide hydrochloride are added. The mixture is stirred at 0° C. for one hour and then at room temperature for 18 hours. The reaction mixture is diluted with dichloromethane (50 ml) and washed successively with water (20 ml), 1N hydrochloric acid (30 ml), saturated aqueous sodium bicarbonate solution (30 ml) and saturated aqueous sodium chloride solution. The organic phase is dried over anhydrous magnesium sulfate. The solution is concentrated under reduced pressure. The residue (1.2 g) is dissolved in 30 ml of ethanol, 0.13 ml (0.61 mmol) of 37% strength hydrochloric acid is added and the mixture is stirred under reflux for one hour. After cooling, 0.59 g (3.18 mmol) of guanidinium carbonate is added and the reaction mixture is stirred at reflux (oil bath temperature 93° C.) for 18 hours. The solution is concentrated. The crude product is purified on a silica gel column using dichloromethane/methanol 20:1. This gives 0.68 g (27% of theory) of product.

المصدر