تفاعل #41168

معادلة التفاعل

Hydrazino-cyclohexanol hydrochloride

Ethyl (ethoxymethylene)-cyanoacetate

sodium acetate

→

5-amino-1-(cis-4-hydroxy-cyclohexyl)-1H-pyrazole-4-carboxylic acid ethyl ester

5-amino-1-(trans-4-hydroxy-cyclohexyl)-1H-pyrazole-4-carboxylic acid ethyl ester

المردود 28.0%

المذيبات

ethanol

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةcooled slightly
2. 2
   درجة الحرارةAfter cooling to room temperature
3. 3
   أخرىthe mixture was partitioned between methylene chloride and water
4. 4
   غسيلThe aqueous phase was washed with a second portion of methylene chloride
5. 5
   غسيلwashed with brine
6. 6
   تجفيفdried over sodium sulfate
7. 7
   تركيزconcentrated
8. 8
   غسيلFlash chromatography, eluting with a 0-20% methanol/ethyl acetate gradient
9. 9
   أخرىseparated
10. 10
    workup.ADDITIONa large portion of the cis-trans mixture of isomers
11. 11
    أخرىcrystallized from EtOAc-hexanes

الإجراء التجريبي

Hydrazino-cyclohexanol hydrochloride (1.920 g, 9.79 mmol) was dissolved in hot ethanol and then cooled slightly. Ethyl (ethoxymethylene)-cyanoacetate (1.520 g, 8.98 mmol) and anhydrous sodium acetate (2.013 g, 24.54 mmol) were added and the mixture was heated at 70° C. for 15 hours. After cooling to room temperature, the mixture was partitioned between methylene chloride and water. The aqueous phase was washed with a second portion of methylene chloride. The two organic phases were combined, washed with brine, dried over sodium sulfate and concentrated. Flash chromatography, eluting with a 0-20% methanol/ethyl acetate gradient, separated a large portion of the cis-trans mixture of isomers. After chromatography, pure fractions of each isomer were combined and crystallized from EtOAc-hexanes to give 5-amino-1-(cis-4-hydroxy-cyclohexyl)-1H-pyrazole-4-carboxylic acid ethyl ester (0.511 g, 23% (crop 1); 0.121 g, 5% (crop 2)) and 5-amino-1-(trans-4-hydroxy-cyclohexyl)-1H-pyrazole-4-carboxylic acid ethyl ester (0.625 g, 28%).

المصدر