反应详情

温度

2.5 °C

In a 500 mL flask was charged (R)-2,3,4,5-tetrahydro-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine-7-carbonitrile (25.0 g, 1 eq.), imidazole-4-carboxaldehyde (6.45 g, 1.1 eq.), and CH2Cl2 (150 mL) at room temperature. Cool to 0-5° C. Add trifluoroacetic acid (18.8 mL, 4 eq.) in a period of 10 min. A solution was obtained after addition. Stir the mixture for 10 min at 2° C. Add trichloroacetic acid anhydride (11.7 mL, 1.05 eq.) in a period of 20 min at 2° C. Stir the mixture for 30 min at 0-5° C. Add Na(OAc)3BH (15.51 g, 1.2 eq.) in two portions at 0-5° C. Agitate the mixture at 0° C. for 1.5 h, then room temperature for 1 hour. Add CH2Cl2 (100 mL), then cool to 0° C. Adjust the pH to 8-9 with 10% NaOH (about 125 mL used). Stir for 30 min. Separate the two phases. Wash the organic phase with H2O (2×100 mL), then separate the two phases. Remove most of the solvents, and add EtOH (200 mL); and heat up to 74° C. Stir for 10 min at 74° C. Cool to room temperature in a period of 60 min. Crystals appeared at 65° C. Filter and wash the crystals with EtOH (40 mL). Dry at 40° C. in vacuum oven over night to give the product (13.55 g, 90.7% yield) as a white solid.

1. customA solution was obtained
2. additionafter addition
3. stirringStir the mixture for 30 min at 0-5° C
4. customat 0-5° C
5. stirringAgitate the mixture at 0° C. for 1.5 h
6. waitroom temperature for 1 hour
7. stirringStir for 30 min
8. customSeparate the two phases
9. washWash the organic phase with H2O (2×100 mL)
10. customseparate the two phases
11. customRemove most of the solvents
12. additionadd EtOH (200 mL)
13. temperatureand heat up to 74° C
14. stirringStir for 10 min at 74° C
15. temperatureCool to room temperature in a period of 60 min
16. customappeared at 65° C
17. filtrationFilter
18. washwash the crystals with EtOH (40 mL)
19. customDry at 40° C. in vacuum oven over night