反应详情

2.77 g (11 mMol) of 3-ethoxy-4-ethoxycarbonylphenylacetic acid are added at ambient temperature to a solution of 2.71 g (11 mMol) of anhydrous (S)-3-methyl-1-(2-piperidino-phenyl)-1-butylamine (ee=98.5%) in 30 ml of absolute toluene and the mixture is stirred until dissolved. Then 2.38 g (11.55 mMol) of N,N'-dicyclohexyl-carbodiimide are added and the mixture is stirred at ambient temperature. After 24 hours a further 0.54 g (2.14 mMol) of 3-ethoxy-4-ethoxycarbonylphenylacetic acid and 0.48 g (2.33 mMol) of N,N'-dicyclohexylcarbodiimide are added and the mixture is stirred overnight. It is then cooled to an internal temperature of +5° C. and suction filtered to separate the precipitate, which is washed once with 5 ml of toluene. The combined toluene filtrates are evaporated down in vacuo to a volume of about 10 ml. The resulting solution is heated over the stem bath and petroleum ether is added in batches thereto (total of 55 ml) until the turbidity remains. It is cooled in ice, whereupon crystallisation takes place. It is suction filtered and dried at 75° C/4 torr. The product obtained (4.57 g; melting point 111°-112° C; ee=98.9%) is suspended in 50 ml of petroleum ether. The mixture is heated over the steam bath and sufficient toluene is added in batches (8 ml in total) until a solution is obtained. This is then cooled in ice and suction filtered to separate the crystals, which are dried at 75° C./4 torr.

1. dissolutionuntil dissolved
2. stirringthe mixture is stirred at ambient temperature
3. stirringthe mixture is stirred overnight
4. temperatureIt is then cooled to an internal temperature of +5° C. and suction
5. filtrationfiltered
6. customto separate the precipitate, which
7. washis washed once with 5 ml of toluene
8. customThe combined toluene filtrates are evaporated down in vacuo to a volume of about 10 ml
9. temperatureThe resulting solution is heated over the stem bath and petroleum ether
10. additionis added in batches
11. temperatureIt is cooled in ice, whereupon crystallisation
12. filtrationfiltered
13. customdried at 75° C/4 torr
14. customThe product obtained (4.57 g; melting point 111°-112° C; ee=98.9%)
15. additionis added in batches (8 ml in total) until a solution
16. customis obtained
17. temperatureThis is then cooled in ice
18. filtrationsuction filtered
19. customto separate the crystals, which
20. customare dried at 75° C./4 torr