反応 #746412

反応方程式

N,N-Diisopropyl ethyl amine

O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

2,4-Bis(trifluoromethyl)-6-methoxy-benzoic acid

cis-2-pyrrolidin-1-yl-cyclohexylamine dihydrochloride

intermediate F

cis-2-pyrrolidin-1-yl-cyclohexylamine dihydrochloride

→

cis-2-methoxy-N-(2-pyrrolidin-1-yl-cyclohexyl)-4,6-bis-trifluoromethyl-benzamide

収率 52.2%

溶媒

dimethylformamide

反応条件

後処理

1. 1
   workup.ADDITIONwas added
2. 2
   その他The solvent was evaporated off
3. 3
   抽出ethyl acetate and was extracted three times with ethyl acetate
4. 4
   その他The combined organic phases were dried on sodium sulfate
5. 5
   ろ過filtered
6. 6
   その他evaporated
7. 7
   その他Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→140:10:1)

実験手順

2,4-Bis(trifluoromethyl)-6-methoxy-benzoic acid (200 mg, 0.69 mmol) was dissolved in 5 mL dimethylformamide. N,N-Diisopropyl ethyl amine (359 mg, 2.8 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (264 mg, 0.69 mmol) were added. After 5 minutes of stirring at room temperature cis-2-pyrrolidin-1-yl-cyclohexylamine dihydrochloride (intermediate F) (171 mg, 0.71 mmol) was added. The reaction mixture was stirred at room temperature overnight. The solvent was evaporated off. The residue was taken up in 2N sodium carbonate solution and ethyl acetate and was extracted three times with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and evaporated. Purification of the residue by flash chromatography on silica gel (dichloromethane/methanol/ammonia 100:0:0→140:10:1) yielded cis-2-methoxy-N-(2-pyrrolidin-1-yl-cyclohexyl)-4,6-bis-trifluoromethyl-benzamide as a white solid (158 mg, 52%), MS: m/e=439.2 [(M+H)+].

出典