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

HRID 8449

Reaction equation

HRID 8449 reaction equation
C[O:2][C:3](=[O:16])[CH:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([F:14])[C:8]=1[F:15])[CH3:5].P([O-])([O-])([O-])=O.Cl>C(Cl)Cl>[F:15][C:8]1[C:9]([F:14])=[C:10]([F:13])[CH:11]=[CH:12][C:7]=1[NH:6][C@H:4]([CH3:5])[C:3]([OH:16])=[O:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 1061PhosphateHCID 22015876Methyl2-(2,3,4-trifluoroanilino)propionate

Product 1

HCID 67366673(2R)-2-(2,3,4-trifluoroanilino)propionic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

Methyl2-(2,3,4-trifluoroanilino)propionate (1.0 g) was suspended in a 0.1 M phosphate buffer solution (pH 6.5; 200 ml). After adding α-chymotrypsin (manufactured by Sigma; 0.2 g), the mixture was gently stirred. The mixture was further stirred for 16 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 (2S)-2-(2,3,4-trifluoroanilino)propionate (0.43 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 (0.47 g). The optical purity of this product was 92% 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 29.

Workup

  1. additionAfter adding α-chymotrypsin (manufactured by Sigma; 0.2 g)
  2. stirringThe mixture was further stirred for 16 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 (2S)-2-(2,3,4-trifluoroanilino)propionate (0.43 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

Sources & evidence

ORD record
ord-d25e9a67e11f44edbe19e5ee44815d44
Source dataset
uspto-grants-2006_08
Patent number
US07087778B2

Linked notes

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