反应详情

8.6 g of magnesium chips was placed in 75 ml of tetrahydrofuran. Then a mixture of 3.2 g of 1,2-dibromoethane and 2.5 g of 1,4-dichlorobutane in 35 ml of tetrahydrofuran was added within 15 minutes so that the temperature could be kept between 30° and 35° C. Then another b 20.5 g of 1,4-dichlorobutane in 75 ml of tetrahydrofuran was added within 30 minutes. The reaction mixture was stirred for 3 hours at this temperature and then mixed with 9 g of tetramethylethylenediamine and 180 ml of tetrahydrofuran. The reaction solution was cooled to -40° to -45° C. and then mixed with a solution of 30 g of (3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno[3,4-d]imidazol-2,4(3H,3aH)-dione in 180 ml of tetrahydrofuran within 20 minutes. It was stirred at this temperature for 1 hour and then CO2 gas was introduced for 30 minutes. The reaction mixture was poured onto 400 ml of 10 percent aqueous sulfuric acid and extracted several times with toluene. The toluene phase was mixed with 0.8 g of conc. sulfuric acid, washed with water and concentrated on a rotary evaporator. The residue was mixed with 400 ml of 10 percent potassium carbonate solution and extracted with ethyl acetate. The organic phase was washed again with 10 percent potassium carbonate solution. The combined aqueous phases were adjusted to pH 7.3 with aqueous sulfuric acid and extracted several times with ethyl acetate. The organic phase was finally dried with magnesium sulfate and concentrated. The product was precipitated by addition of hexane, filtered off and dried. 32.5 g (89.3 percent) of the title product was obtained as snow-white powder with a content (HPLC) of more than 99 percent. Concerning the product: Melting point: 101.0°-102.0° C.

1. additionwas added within 15 minutes so that the temperature
2. customcould be kept between 30° and 35° C
3. temperatureThe reaction solution was cooled to -40° to -45° C.
4. stirringIt was stirred at this temperature for 1 hour
5. extractionextracted several times with toluene
6. additionThe toluene phase was mixed with 0.8 g of conc. sulfuric acid
7. washwashed with water
8. concentrationconcentrated on a rotary evaporator
9. additionThe residue was mixed with 400 ml of 10 percent potassium carbonate solution
10. extractionextracted with ethyl acetate
11. washThe organic phase was washed again with 10 percent potassium carbonate solution
12. extractionextracted several times with ethyl acetate
13. dry with materialThe organic phase was finally dried with magnesium sulfate
14. concentrationconcentrated
15. customThe product was precipitated by addition of hexane
16. filtrationfiltered off
17. customdried