反应详情

温度

-78 °C

Hydrazine hydrate (4.77 mL, 153.4 mmol) was placed in a three neck flask fitted with an overhead stirring rod and a reflux condenser and cooled in a dry ice acetone bath at −78° C. After the solution reached −50° C. the bath was removed and (4-cyclopropylsulfanyl-phenyl)-oxo-acetic acid (3.41 g, 15.34 mmol) was added in one portion. The temperature increased due to an exotherm and it was then heated in an oil bath to 80° C. After the reaction was at 80° C. it was treated with potassium hydroxide (593 mg, 9.20 mmol) and stirred vigorously. When the reaction returned to 80° C. a second portion of potassium hydroxide (593 mg, 9.20 mmol) was added and allowed to cool back to 80° C. This cycle was repeated two more times adding potassium hydroxide (593 mg, 9.20 mmol) each time. The reaction was then heated at 100° C. for 16 h over which time the reaction became a homogenous clear yellow solution. It was 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) was added and diethyl ether (10 mL). The layers were separated and the aqueous layer separated into a flask. The organic layer was then extracted with water (5 mL) and this aqueous layer combined with the first. To the aqueous layers was then added heptane (5 mL) and stirred vigorously. This solution was cooled to 0° C. in an ice bath and was treated dropwise with concentrated hydrochloric acid (˜7 mL) over 30 min until the aqueous layer was at pH=2 keeping the temperature of the solution below 50° C. during the addition process and it turned cloudy. It was then allowed to cool to 25° C. and stirred for 3 h. It was then filtered to remove the solids and the solids were 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 was then dried in a vacuum oven to afford (4-cyclopropylsulfanyl-phenyl)-acetic acid (2.70 g, 85%) as a yellow solid.

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