Hydrochloric Acid → (2S)-2-(2,3,4-trifluoroanilino)propionic acid

Temperature

30 °C

Methyl 2-(2,3,4-trifluoroanilino)propionate (2.0 g) was suspended in a 0.1 M phosphate buffer solution (pH 6.5; 400 ml). After adding Protease N (manufactured by Amano Seiyaku, originating in a bacterium belonging to the genus Bacillus; 0.4 g), the mixture was gently stirred. The mixture was further stirred for 14 hours while maintaining at 30° C. After adding methylene chloride, the liquid reaction mixture was filtered through celite to eliminate denatured protein and then separated. The organic layer was washed with a 5% aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. Next, the solvent was evaporated under reduced pressure to thereby give methyl (2R)-2-(2,3,4-trifluoroanilino)propionate (0.94 g). The optical purity of this product was 98% ee. On the other hand, the all aqueous layers obtained by the separation were combined and adjusted to pH 2 with 10% hydrochloric acid followed by extraction with IPE. The organic layer was dried over anhydrous magnesium sulfate and evaporated. Thus, the title compound was obtained as a crude product (0.96 g). The optical purity of this product was 96% ee. Further, the crude product was recrystallized from a solvent mixture of isopropyl ether with hexane. Thus, the title compound of 100% ee was obtained. The 1H-NMR and IR spectral data of this product was identical with those of the compound obtained in Example 28.

1. additionAfter adding Protease N (
2. stirringThe mixture was further stirred for 14 hours
3. customthe liquid reaction mixture
4. filtrationwas filtered through celite
5. customseparated
6. washThe organic layer was washed with a 5% aqueous solution of sodium hydrogencarbonate
7. dry with materiala saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate
8. customNext, the solvent was evaporated under reduced pressure to thereby give methyl (2R)-2-(2,3,4-trifluoroanilino)propionate (0.94 g)
9. customOn the other hand, the all aqueous layers obtained by the separation
10. extractionfollowed by extraction with IPE
11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
12. customevaporated

ORD record

ord-4422656219334b068b517b82fbb0d016

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087778B2