반응 #72222

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Water

lithium hydroxide

Methyl cis(±)-5-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-methylthiophene-2-carboxylate

THF

→

title compound

수율 37.0%

cis(±)-5-(4-{[(4-Chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-methylthiophene-2-carboxylic acid

수율 37.0%

용매

methanol

반응 조건

후처리

1. 1
   workup.STIRRINGthe mixture was stirred for 19 hours
2. 2
   workup.STIRRINGfurther stirred at 40° C. for 6.5 hours and at 70° C. for two hours
3. 3
   세척the mixture was washed with ethyl acetate
4. 4
   workup.ADDITIONA 1 N aqueous hydrochloric acid solution (2.5 mL) was added to the aqueous layer
5. 5
   추출followed by extraction with ethyl acetate
6. 6
   건조The combined organic layers were dried over anhydrous magnesium sulfate
7. 7
   여과filtered
8. 8
   농축the filtrate was concentrated under reduced pressure
9. 9
   세척washed in diethyl ether

실험 절차

Methyl cis(±)-5-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-3-methylthiophene-2-carboxylate obtained in Example (245d) (65 mg, 0.15 mmol) was dissolved in methanol (1.5 mL). A 2 N aqueous lithium hydroxide solution (0.74 mL, 1.47 mmol) was added, and the mixture was stirred at room temperature for 50 minutes. THF (1 mL) was added, and the mixture was stirred for 19 hours, and then further stirred at 40° C. for 6.5 hours and at 70° C. for two hours. Water was added to the reaction solution, and then the mixture was washed with ethyl acetate. A 1 N aqueous hydrochloric acid solution (2.5 mL) was added to the aqueous layer, followed by extraction with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The resulting solid was suspended and washed in diethyl ether to obtain 23 mg of the title compound as a pale blue solid (37%).

출처