Water → (3-Chloro-4-cyclopentylsulfanyl-phenyl)-acetic acid

温度

-78 °C

Hydrazine hydrate (10 equiv.) is placed in a three neck flask fitted with an overhead mechanical stirrer and a reflux condenser and cooled in a dry ice acetone bath at −78° C. After the solution reached −50° C. the bath is removed and (3-chloro-4-cyclopentylsulfanyl-phenyl)-oxo-acetic acid (15.00 mmol) is added in one portion. It is then heated in an oil bath to 80° C. After the reaction is at 80° C. it is treated with potassium hydroxide (0.60 equiv.) and stirred vigorously. When the reaction returns to 80° C. a second portion of potassium hydroxide (0.60 equiv.) is added and allowed to cool back to 80° C. This cycle is repeated two more times adding potassium hydroxide (0.60 equiv.) each time. The reaction is then heated at 100° C. for 16 h. It is then cooled to 25° C. and water (3 mL) added to the reaction. It was then transferred to a separatory funnel and another portion of water (3 mL) is added and diethyl ether (10 mL). The layers are separated and the aqueous layer separated into a flask. The organic layer is then extracted with water (5 mL) and this aqueous layer combined with the first. To the aqueous layer is then added heptane (5 mL) and stirred vigorously. This solution is cooled to 0° C. in an ice bath and is treated dropwise with concentrated hydrochloric acid (˜7 mL) over 30 min until the aqueous layer is at pH=2 keeping the temperature of the solution below 50° C. during the addition process. It is then allowed to cool to 25° C. and stirred for 3 h. It is then filtered to remove the solids and the solids are washed with 1N aqueous hydrochloric acid (1.5 mL), water (2×1.5 mL), heptane (5 mL) and 1:1 heptane:diethyl ether (5 mL) and the solid is then dried in a vacuum oven to afford (3-chloro-4-cyclopentylsulfanyl-phenyl)-acetic acid.

1. customfitted with an overhead mechanical stirrer and a reflux condenser
2. customreached −50° C.
3. customis removed
4. temperatureIt is then heated in an oil bath to 80° C
5. customis at 80° C.
6. customreturns to 80° C.
7. additionis added
8. temperatureto cool back to 80° C
9. temperatureThe reaction is then heated at 100° C. for 16 h
10. temperatureIt is then cooled to 25° C.
11. customIt was then transferred to a separatory funnel
12. customThe layers are separated
13. customthe aqueous layer separated into a flask
14. extractionThe organic layer is then extracted with water (5 mL)
15. stirringadded heptane (5 mL) and stirred vigorously
16. temperatureThis solution is cooled to 0° C. in an ice bath
17. additionis treated dropwise with concentrated hydrochloric acid (˜7 mL) over 30 min until the aqueous layer
18. customthe temperature of the solution below 50° C.
19. temperatureto cool to 25° C.
20. stirringstirred for 3 h
21. filtrationIt is then filtered
22. customto remove the solids
23. washthe solids are washed with 1N aqueous hydrochloric acid (1.5 mL), water (2×1.5 mL), heptane (5 mL) and 1:1 heptane
24. dry with materialdiethyl ether (5 mL) and the solid is then dried in a vacuum oven

ORDレコード

ord-3f8351d4397648da8afbd02adb9552d2

出典データセット

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07935699B2