Sodium Hydroxide → HCID 13728676, compound

HRID 1905081Notes

Reaction equation

HRID 1905081 reaction equation
[NH2:1][C:2]1([C:13]([O:15][CH3:16])=[O:14])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[O:5][CH2:4][CH2:3]1.[OH-].[Na+]>[Cl-].[Na+].Cl>[NH2:1][C@:2]1([C:13]([O:15][CH3:16])=[O:14])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[O:5][CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 13728675Methyl 4-amino-6-fluoro-3,4-dihydro-2H-1-benzopyran-4-carboxylate

Product 1

HCID 13728676HCID 13728676, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolvent2×HCID 5234Sodium ChlorideSolvent

Procedure

Methyl 4-amino-6-fluorochroman-4-carboxylate (11.5 g., 0.051 mole), the racemic spiro-amino acid methyl ester prepared in Example 20, was dissolved in 0.125 M aqueous sodium chloride solution (100 ml.) at pH 5 by the addition of 6N hydrochloric acid. α-Chymotrypsin (750 mg.), available from the Sigma Chemical Company of St. Louis, Mo., was then added to the mixture with stirring at room temperature (~20° C.). After an initial induction period of several hours, hydrolysis commenced as evidenced by the uptake of 0.5 N aqueous sodium hydroxide from a pHstat to maintain the pH of the reaction solution at pH 5.1. The reaction was then continued until the uptake of base ceased. The reaction mixture was then acidified with 6 N hydrochloric acid to pH 2 and activated carbon (1 g.) was added. After stirring for two hours, supercel (0.5 g.) was added and stirring was continued for another three hours. The spent reaction mixture was then filtered through supercel and extracted with ethyl acetate. The aqueous layer so obtained was adjusted to pH 10 with 6 N aqueous sodium hydroxide and thereafter extracted with ethyl acetate (three times). The combined organic layers were then washed with brine and dried over anhydrous magnesium sulfate. After removal of the drying agent by means of filtration and the solvent by means of evaporation under reduced pressure, there were obtained 4.17 g. of pure (S)-methyl 4-amino-6-fluorochroman-4-carboxylate (73%) yield based on available enantiomer) in the form of a colorless oil, [α]D25° +51.2°(c=0.64, CHCl3); NMR (CDCl3) identical with the racemic amino acid ester.

Workup

  1. addition, was then added to the mixture
  2. customAfter an initial induction period of several hours, hydrolysis
  3. temperatureto maintain the pH of the reaction solution at pH 5.1
  4. additionwas added
  5. stirringAfter stirring for two hours
  6. additionsupercel (0.5 g.) was added
  7. stirringstirring
  8. customThe spent reaction mixture
  9. filtrationwas then filtered through supercel
  10. extractionextracted with ethyl acetate
  11. customThe aqueous layer so obtained
  12. extractionextracted with ethyl acetate (three times)
  13. washThe combined organic layers were then washed with brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customAfter removal of the drying agent
  16. filtrationby means of filtration
  17. customthe solvent by means of evaporation under reduced pressure
  18. customthere were obtained 4.17 g

Sources & evidence

ORD record
ord-38fc97bc8d4146a2ac51d3e4a8df9dbf
Source dataset
uspto-grants-1989_06
Patent number
US04841079

Reaction notes

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