反応 #155672

反応方程式

C-pyridine-2-yl-methylamine

CDI

pyrrolidine-1-carboxylic acid (4-hydroxy-cyclohexylmethyl)-amide

methyl iodide

→

compound

収率 25.0%

pyridin-4-ylmethyl-carbamic acid 4-{[(pyrrolidine-1-carbonyl)-amino]-methyl}-cyclohexyl ester

収率 25.0%

溶媒

water

acetonitrile

反応条件

後処理

1. 1
   workup.STIRRINGstirred for additional 1 hour at 80° C
2. 2
   濃縮The reaction mixture was concentrated under reduced pressure
3. 3
   workup.DISSOLUTIONthe residue was dissolved in acetonitrile (10 mL)
4. 4
   workup.STIRRINGAfter 4 hours stirring at 80° C.
5. 5
   抽出followed by few times of extraction with methylene chloride
6. 6
   乾燥The combined organic layer was dried over anhydrous magnesium sulfate
7. 7
   ろ過filtered
8. 8
   濃縮concentrated under reduced pressure
9. 9
   その他The residue was purified by column chromatography (silica gel, hexane:ethyl acetate=1:3)

実験手順

To a solution of 4-hydroxymethylcyclohexanol (2 mmol) in THF (10 mL) were added Ms-Cl (2.2 mmol) and triethylamine (3 mmol) at 0° C. and the resulting mixture was stirred for 2 hours. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in 10 mL of DMF, and then NaN3(6 mmol) was added. After overnight stirring at 60° C., the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Then, the obtained compound was dissolved in methanol, and 10% Pd—C (0.2 mmol) was added. After overnight stirring under hydrogen atmosphere, the reaction mixture was filtered, washed with methanol and concentrated under reduced pressure to provide 4-aminomethyl-cyclohexanol. To a solution of 4-aminomethyl-cyclohexanel in dichloromethane (10 mL) were added 1-pyrrolidinecarbonyl chloride (2 mmol) and triethylamine (3 mmol). After overnight stirring at room temperature, the reaction mixture was diluted with water, followed by few times of extraction with methylene chloride. The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, hexane:ethyl acetate=1:1) to provide a pyrrolidine-1-carboxylic acid (4-hydroxy-cyclohexylmethyl)-amide. The pyrrolidine-1-carboxylic acid (4-hydroxy-cyclohexylmethyl)-amide compound was dissolved in acetonitrile (10 mL), and then CDI (2.2 mmol) was added. After 1 hours stirring at 80° C., methyl iodide (10 mmol) was added and stirred for additional 1 hour at 80° C. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in acetonitrile (10 mL) and C-pyridine-2-yl-methylamine (3 mmol) was added. After 4 hours stirring at 80° C., the reaction mixture was diluted with water, followed by few times of extraction with methylene chloride. The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, hexane:ethyl acetate=1:3), thereby completing the preparation of a target compound (180 mg, 25% yield).

出典