反应详情

温度

20 °C

N-[2-(2-Isobutyl-3-oxo-5-trifluoromethyl-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is prepared as described in Example 9, starting with 10 cm3 of absolute ethanol, 0.19 g of sodium, 0.78 g of guanidinium chloride and 1.86 g of ethyl (5-trifluoromethyl-2-isobutyl-3-oxo-2,3-dihyrdo-1H-isoindol-1-yl)acetate in 10 cm3 of absolute ethanol. The reaction mixture is stirred at a temperature in the region of 20° C. for 16 hours and is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is then taken up in a mixture of 5 cm3 of water and 15 cm3 of diethyl ether and then concentrated to dryness again under the same conditions. The residue is taken up in 100 cm3 of ethyl acetate and the organic phase is washed with twice 60 cm3 of aqueous 1N sodium hydroxide solution and then with twice 60 cm3 of 4N hydrochloric acid solution. The acidic aqueous extracts are combined, treated with aqueous 30% sodium hydroxide solution to pH 14, and then extracted with 3 times 50 cm3 of ethyl acetate. The organic extracts are combined, washed with 100 cm3 of saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The yellow solid thus obtained is taken up in 20 cm3 of diethyl ether, stirred at a temperature in the region of 20° C. for 1 hour and then filtered off. The solid is washed with twice 20 cm3 of diethyl ether and then dried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 35° C. 0.34 g of N-[(5-trifluoromethyl-2-isobutyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)acetyl]guanidine is thus obtained in the form of a yellow powder melting at 224° C. (Analysis: C16 H19 F3 N4 O2% calculated C, 53.93; H, 5.37; F, 15.99; N, 15.72; O, 8.98%. found C, 53.95; H, 5.15; F, 15.00; N, 15.59).

1. customN-[2-(2-Isobutyl-3-oxo-5-trifluoromethyl-2,3-dihydro-1H-isoindol-1-yl)-acetyl]-guanidine is prepared
2. concentrationis then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
3. additionThe residue is then taken up in a mixture of 5 cm3 of water and 15 cm3 of diethyl ether
4. concentrationconcentrated to dryness again under the same conditions
5. washthe organic phase is washed with twice 60 cm3 of aqueous 1N sodium hydroxide solution
6. additiontreated with aqueous 30% sodium hydroxide solution to pH 14
7. extractionextracted with 3 times 50 cm3 of ethyl acetate
8. washwashed with 100 cm3 of saturated sodium chloride solution
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
11. customThe yellow solid thus obtained
12. stirringstirred at a temperature in the region of 20° C. for 1 hour
13. filtrationfiltered off
14. washThe solid is washed with twice 20 cm3 of diethyl ether
15. customdried in a desiccator under reduced pressure (2 Pa) at a temperature in the region of 35° C