4-Toluenesulfonyl chloride → 4-(2-Piperidinoethoxy)benzoic acid hydrochloride

温度

145 °C

Into a 50 ml round bottom flask is placed 6.40 g (33.6 mmol) of p-toluenesulfonyl chloride and 25 ml of methylene chloride. The resulting solution is cooled with an ice bath as 4.00 g (31.0 mmol) of 1-piperidinoethanol in 6 ml of methylene chloride is added dropwise. After the addition is complete, the ice bath is removed and the resulting slurry is stirred for about 12 hours. The reaction mixture is concentrated on a rotary evaporator to yield a solid residue. The solid residue is transferred to a 100 ml round bottom flask with 45 ml of amyl acetate. Potassium carbonate (6.87 g, 49.7 mmol) and methyl 4-hydroxybenzoate (2.82 g, 18.5 mmol) are added to the slurry. The resulting mixture is heated to 145° C. for 2 hours. The reaction mixture is cooled to room temperature and washed twice with water. The organic layer is extracted with 11 ml of 8 N hydrochloric acid. The aqueous layer is heated at gentle reflux for 3 hours. The resulting slurry is cooled to 50° C. and 11 ml of acetone is added. The slurry is cooled to 0-5°0 C. and stirred for 1 hour. The product is filtered, washed with cold acetone, and dried at 50° C. in vacuo to yield 920 mg of product, (17%). 1H NMR. Potency 97.6%. TRS 1.16%

1. customInto a 50 ml round bottom flask is placed
2. additionis added dropwise
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 water
9. extractionThe organic layer is extracted with 11 ml of 8 N hydrochloric acid
10. temperatureThe aqueous layer is heated
11. temperatureat gentle reflux for 3 hours
12. temperatureThe resulting slurry is cooled to 50° C.
13. addition11 ml of acetone is added
14. temperatureThe slurry is cooled to 0-5°0 C
15. stirringand stirred for 1 hour
16. filtrationThe product is filtered
17. washwashed with cold acetone
18. customdried at 50° C. in vacuo

ORDレコード

ord-fdd0d51b2f09488a93c16e3493053966

出典データセット

uspto-grants-2000_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06075146