反应详情

温度

0 °C

(S)-Methyl 3-amino-3-(4-fluorophenyl)propionate hydrochloride (4.5 g) was dissolved in THF (30 ml) and cooled to 0° C. After the addition of diisopropylethylamine (8.8 g), benzyl chloroformate (4.3 g) was slowly added dropwise and the mixture was stirred at 0° C. for 1 hour. The reaction mixture was concentrated by rotary evaporation, dichloromethane (50 ml) was added and the mixture was washed twice with NH4Cl solution. Subsequently, the organic phase was dried with MgSO4, filtered and concentrated. The residue (5.72 g) was taken up in THF, titanium tetraisopropoxide (0.49 g) was added, and ethylmagnesium bromide (3 N, 17.9 ml) was added dropwise over the course of 1 hour. After 24 hours, the reaction solution was poured into cold 2 N sulfuric acid (150 ml) and extracted three times with dichloromethane. The combined organic phases were dried with MgSO4, filtered and concentrated. The residue was purified by preparative HPLC. The resulting (S)-1-(4-fluorophenyl)-2-(1-hydroxycyclopropyl)ethyl]carbamic acid benzyl ester (0.76 g) was dissolved in methanol (20 ml), 5% Pd/C was added and hydrogenation was effected under hydrogen pressure 2 bar. After filtration and concentration, the product (87 mg) was thus obtained with a molecular weight of 329.3 g/mol (C19H20FNO3), MS (ESI): m/e=330 (M+H+).

1. additionwas slowly added dropwise
2. concentrationThe reaction mixture was concentrated by rotary evaporation, dichloromethane (50 ml)
3. additionwas added
4. washthe mixture was washed twice with NH4Cl solution
5. dry with materialSubsequently, the organic phase was dried with MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. additiontitanium tetraisopropoxide (0.49 g) was added
9. additionethylmagnesium bromide (3 N, 17.9 ml) was added dropwise over the course of 1 hour
10. waitAfter 24 hours
11. additionthe reaction solution was poured into cold 2 N sulfuric acid (150 ml)
12. extractionextracted three times with dichloromethane
13. dry with materialThe combined organic phases were dried with MgSO4
14. filtrationfiltered
15. concentrationconcentrated
16. customThe residue was purified by preparative HPLC
17. dissolutionThe resulting (S)-1-(4-fluorophenyl)-2-(1-hydroxycyclopropyl)ethyl]carbamic acid benzyl ester (0.76 g) was dissolved in methanol (20 ml)
18. addition5% Pd/C was added
19. filtrationAfter filtration and concentration