反应详情

温度

-20 °C

To a suspension of N-(9-fluorenylmethoxycarbonyl)-D-alanine (21.61 g, 69.4 mmol), methylene chloride (230 ml) and N,N-dimethylformamide (0.37 ml) is added dropwise oxalyl chloride (6.46 ml, 74.0 mmol) at room temperature with stirring, and the mixture is further stirred for 2 hours. The reaction solution is concentrated to dryness under reduced pressure to give an oil containing N-(9-fluorenylmethoxy-carbonyl)-D-alanyl chloride. A solution of 1H-indole-7-carboxylic acid diethylamide (10.0 g, 46.3 mmol) in methylene chloride (120 ml) is cooled to −20° C., and thereto is added dropwise a 3M solution of methyl magnesium bromide/diethyl ether (54 ml, 162 mmol). After the addition, the mixture is further stirred at −20° C. for 2 hours. This reaction solution is cooled to −25-−15° C., and thereto is added dropwise a solution of the above obtained N-(9-fluorenylmethoxycarbonyl)-D-alanyl in methylene chloride (140 ml), and the mixture is further stirred at −20° C. for 2 hours. The mixture is warmed to about −5° C., and poured into 2N hydrochloric acid. The organic layer is separated, washed with water (25 ml) and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure, and the residue is purified by silica gel column chromatography (ethyl acetate/hexane=1/2→5/1) to give the desired (R)-[2-(7-diethylcarbamoyl-1H-indol-3-yl)-1-methyl-2-oxoethyl]carbamic acid 9H-fluoren-9-ylmethyl ester (10.24 g, yield: 43%).

1. stirringthe mixture is further stirred for 2 hours
2. concentrationThe reaction solution is concentrated to dryness under reduced pressure
3. customto give an oil
4. additionAfter the addition
5. stirringthe mixture is further stirred at −20° C. for 2 hours
6. additionis added dropwise a solution of the
7. stirringthe mixture is further stirred at −20° C. for 2 hours
8. temperatureThe mixture is warmed to about −5° C.
9. customThe organic layer is separated
10. washwashed with water (25 ml)
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent is evaporated under reduced pressure
13. customthe residue is purified by silica gel column chromatography (ethyl acetate/hexane=1/2→5/1)