反应详情

温度

90 °C

With ice cooling, a suspension of 2-amino-2-fluoromethyl-3-(4-hydroxyphenyl)propionic acid (10.0 g) in absolute methanol (400 ml, dried over magnesium) is saturated with HCl gas. After heating at 90° C. overnight, the solvent is removed under reduced pressure, and the residue is dried for 3 hours under the vacuum of an oil pump. After dissolving in absolute methanol (400 ml) and saturating with HCl gas, the mixture is heated at 90° C. overnight again. After evaporation of the solvent, the residue is dissolved in water and a solution of sodium carbonate is added with stirring until pH~10. The suspension is extracted 3 times with ether; the combined ether extracts are filtered, washed carefully with water, dried (Na2SO4) and evaporated to give pure methyl 2-amino-2-fluoromethyl-3-(4-hydroxyphenyl)propionate (7.5 g, 70%) as white crystals, m.p. 130° C.; NMR (CD3OD): δ2.77 (2H, AB, JAB =14 Hz), 3.70 (3H, s), 4.50 (2H, ABX, JAB =9 Hz, JAX =JBX =JH--F =46 Hz), 6.87 (4H, A2B2 with additional fine splitting, JAB =9 Hz).

1. customthe solvent is removed under reduced pressure
2. customthe residue is dried for 3 hours under the vacuum of an oil pump
3. dissolutionAfter dissolving in absolute methanol (400 ml)
4. concentrationsaturating with HCl gas
5. temperaturethe mixture is heated at 90° C. overnight again
6. customAfter evaporation of the solvent
7. dissolutionthe residue is dissolved in water
8. additiona solution of sodium carbonate is added
9. extractionThe suspension is extracted 3 times with ether
10. filtrationthe combined ether extracts are filtered
11. washwashed carefully with water
12. dry with materialdried (Na2SO4)
13. customevaporated