反应详情

温度

135 °C

Into a 500 ml round bottom flask is placed 23.38 g (197 mmol) of thionyl chloride and 140 ml of methylene chloride. The resulting solution is cooled with an ice bath as 21.91 g (170 mmol) of 1-piperidinoethanol in 30 ml of methylene chloride is added over 30 minutes. After the addition is complete, the ice bath is removed and the mixture is stirred for about 12 hours. The reaction mixture is concentrated on a rotary evaporator to yield a solid residue. Amyl acetate (225 ml), potassium carbonate (34.4 g, 249 mmol), and methyl 4-hydroxybenzoate (14.1 g, 92 mmol) are added to the residue. The resulting slurry is heated to 135° C. for 5 hours. The reaction mixture is cooled to room temperature and washed twice with 100 ml of water. The organic layer is extracted with 53 ml of 8 N hydrochloric acid. The aqueous layer is heated at gentle reflux for 4 hours. The resulting slurry is cooled to 50° C. and 50 ml of acetone is added. The slurry is cooled to 0-5° C. and stirred for 1 hour. The product is filtered, washed with cold acetone, and dried at 50° C. in vacuo to yield 17.9 g of product, (67%). 1H NMR. Compares to reference solution: HPLC potency 97.9%, TRS 1.50% .

1. customInto a 500 ml round bottom flask is placed
2. additionis added over 30 minutes
3. additionAfter the addition
4. customthe ice bath is removed
5. concentrationThe reaction mixture is concentrated on a rotary evaporator
6. customto yield a solid residue
7. temperatureThe reaction mixture is cooled to room temperature
8. washwashed twice with 100 ml of water
9. extractionThe organic layer is extracted with 53 ml of 8 N hydrochloric acid
10. temperatureThe aqueous layer is heated
11. temperatureat gentle reflux for 4 hours
12. temperatureThe resulting slurry is cooled to 50° C.
13. addition50 ml of acetone is added
14. temperatureThe slurry is cooled to 0-5° C.
15. stirringstirred for 1 hour
16. filtrationThe product is filtered
17. washwashed with cold acetone
18. customdried at 50° C. in vacuo