反应详情

A quantity of 438 ml of borane-tetrahydrofuran complex (1M solution in THF, 438 mmol) was introduced with ice cooling. Then 35 g (110 mmol) of N-Boc-2-(3-trifluoromethylphenyl)-DL-glycine were added in portions. The reaction mixture was stirred at RT for 2 h and then cautiously admixed with pieces of ice. After the end of the evolution of gas, the solvent was removed on a rotary evaporator. The aqueous residue was admixed with saturated sodium hydrogen carbonate solution and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and freed from the solvent on a rotary evaporator. The residue was taken up in acetonitrile and 2.5% strength aqueous sodium hydrogen carbonate solution. Then 25.18 ml (109.62 mmol) of di-tert-butyl dicarbonate were added and the mixture was stirred at RT for 3 h. The acetonitrile was removed on a rotary evaporator. The residue was extracted three times with ethyl acetate, dried over sodium sulphate, filtered and freed from the solvent on a rotary evaporator. The residue was again admixed with 438 ml of borane-tetrahydrofuran complex (1M solution in THF, 438 mmol) and stirred at 70° C. for 3 h. It was worked up again, and an excess of a 4N solution of hydrogen chloride in dioxane was added to the complete work-up mixture, which was stirred overnight. Thereafter the solvent was removed on a rotary evaporator. The residue was dried in an HV and then admixed once again with 400 ml of borane-tetrahydrofuran complex (1M solution in THF, 400 mmol) and stirred overnight. It was then worked up and again, as described above, reacted with 25.18 ml (109.62 mmol) of di-tert-butyl dicarbonate. The crude product obtained after work-up was purified by preparative HPLC. Drying in an HV gave 10.2 g (29% of theory) of the title compound.

1. customAfter the end of the evolution of gas, the solvent was removed on a rotary evaporator
2. extractionextracted three times with ethyl acetate
3. dry with materialThe combined organic phases were dried over sodium sulphate
4. customfreed from the solvent on a rotary evaporator
5. stirringthe mixture was stirred at RT for 3 h
6. customThe acetonitrile was removed on a rotary evaporator
7. extractionThe residue was extracted three times with ethyl acetate
8. dry with materialdried over sodium sulphate
9. filtrationfiltered
10. customfreed from the solvent on a rotary evaporator
11. stirringstirred at 70° C. for 3 h
12. stirringwas stirred overnight
13. customThereafter the solvent was removed on a rotary evaporator
14. customThe residue was dried in an HV
15. stirringstirred overnight
16. customThe crude product obtained after work-up
17. customwas purified by preparative HPLC
18. customDrying in an HV