反应详情

Combine (S)-1-(5-bromopyrimidin-2-yl)-pyrrolidine-3-amine (10.0 g, 35.84 mmol) and 30% aqueous sodium hydroxide (1.18 equiv., 4 mL) in water (30 mL), THF (75 mL), and toluene (75 mL). Separate the layers, extract the aqueous layer with 1:1 THF:toluene (50 mL). Combine the organic layers and extract with water (10 mL). Evaporate the organic layer at reduced pressure to give a residue. Combine the residue and toluene (75 mL) and evaporate at reduced pressure to give a residue. Again, combine the residue and toluene (75 mL) and evaporate at reduced pressure to give a residue Combine the residue and toluene (12.9 g) and dry THF (53.2 g), add 2,4-dichlorobenzaldehyde (0.94 equivalent, 33.6 mmol, 6.0 g), and stir. After 1 hour, add sodium triacetoxyborohydride (65.9 mmol, 2.5 equiv., 14.4 g) in 5 portions over about 50 minutes. After 22 hours, slowly add water (16 mL), Stir for 2 hours and then basify to pH=14 by addition of 30% aqueous sodium hydroxide (20 mL). Separate the aqueous layer and extract with 1/1 toluene/THF (120 mL). Combine the organic layers and extract with water (30 mL). Evaporate the solvents at reduced pressure to give a residue. Combine the residue and isopropanol (130 mL) and evaporate at reduced pressure to give a residue. Twice more, combine the residue and isopropanol (130 mL) and evaporate at reduced pressure to give a mass of about 90 g. Slowly cool to room temperature and agitate for about 3 hours to give a solid. Collect the solid by filtration, rinse with isopropanol (10 mL), and dry at 40° C. under vacuum for 15 hours to give the title compound.

1. customSeparate the layers
2. extractionextract the aqueous layer with 1:1 THF
3. extractionCombine the organic layers and extract with water (10 mL)
4. customEvaporate the organic layer at reduced pressure
5. customto give a residue
6. customevaporate at reduced pressure
7. customto give a residue
8. customevaporate at reduced pressure
9. customto give a residue Combine the residue and toluene (12.9 g) and dry THF (53.2 g)
10. waitAfter 22 hours
11. customSeparate the aqueous layer
12. extractionextract with 1/1 toluene/THF (120 mL)
13. extractionCombine the organic layers and extract with water (30 mL)
14. customEvaporate the solvents at reduced pressure
15. customto give a residue
16. customevaporate at reduced pressure
17. customto give a residue
18. customevaporate at reduced pressure
19. customto give a mass of about 90 g
20. stirringagitate for about 3 hours
21. customto give a solid
22. customCollect the solid
23. filtrationby filtration
24. washrinse with isopropanol (10 mL)
25. customdry at 40° C. under vacuum for 15 hours