反应详情

温度

0 °C

A solution of the product of Example 61B (2.26 g) in dichloromethane (20 mL) was treated with oxalyl chloride (5.4 mL, 1.5 equivalents) at −78° C., and stirred for 15 min. DMSO (1.02 mL, 2 equivalents) was added dropwise at −78° C., stirred for 15 min, and quenched with triethylamine (4 mL, 4 equivalents) as the mixture warmed to 0° C. The mixture was quenched with 20% KH2PO4, and partitioned between dichloromethane and water. The organic layer was washed with brine, dried over Na2SO4, and the solvents were evaporated. To this crude product was added methanol/water (7:2), (L)-valine methyl ester (1.21 g, 1 equivalent), sodium acetate trihydrate (1.96 g, 2 equivalents), and NaCNBH3 (0.95 g, 2 equivalents) was added portionwise over 30 min. After stirring for 1 hour, the mixture was partitioned between saturatued NaHCO3, and extracted with ethyl acetate (2×). The combined organic layer was washed with brine, dried with Na2SO4, filtered, and evaporated. The residue was treated with dichloromethane/trifluoacetic acid (10 mL, 1:1), stirred at 25° C. for 2 hrs and concentrated to give the title compound isolated as the trifluoroacetic acid salt.

1. stirringstirred for 15 min
2. customThe mixture was quenched with 20% KH2PO4
3. custompartitioned between dichloromethane and water
4. washThe organic layer was washed with brine
5. dry with materialdried over Na2SO4
6. customthe solvents were evaporated
7. additionwas added portionwise over 30 min
8. stirringAfter stirring for 1 hour
9. customthe mixture was partitioned between saturatued NaHCO3
10. extractionextracted with ethyl acetate (2×)
11. washThe combined organic layer was washed with brine
12. dry with materialdried with Na2SO4
13. filtrationfiltered
14. customevaporated
15. additionThe residue was treated with dichloromethane/trifluoacetic acid (10 mL, 1:1)
16. stirringstirred at 25° C. for 2 hrs
17. concentrationconcentrated