Hydrochloric Acid → N-Phthalimido-3-(3-thienyl)-L-alanine

HRID 260218Notes

Reaction equation

HRID 260218 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([CH2:6][C@@H:7]([C:9]([OH:11])=[O:10])[NH2:8])=[CH:2]1.C(=O)([O-])[O-].[Na+].[Na+].C([N:23]1[C:27](=[O:28])[C:26]2=[CH:29][CH:30]=[CH:31][CH:32]=[C:25]2[C:24]1=[O:33])(OCC)=O.Cl>O.O1CCOCC1>[C:27]1(=[O:28])[N:23]([NH:8][C@H:7]([C:9]([OH:11])=[O:10])[CH2:6][C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)[C:24](=[O:33])[C:25]2=[CH:32][CH:31]=[CH:30][CH:29]=[C:26]12

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 31187N-CarbethoxyphthalimideHCID 819083(alphaS)-alpha-Amino-3-thiophenepropanoic acid

Product 1

HCID 70049552N-Phthalimido-3-(3-thienyl)-L-alanine

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

3-(3-Thienyl)-L-alanine (2.45 g., 14.3 mmol.) was suspended in water/p-dioxane (22 ml/11 ml.) at room temperature under argon. Sodium carbonate (1.52 g.) was added and the mixture was stirred until homogeneous. N-Carbethoxyphthalimide (3.14 g.) was added, and the resulting mixture was stirred for 3.0 hours and then cooled to 0° C. The pH was adjusted to 1.5 with 6N hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 10% potassium bisulfate and brine, dried (sodium sulfate), filtered, and concentrated. The crude product was flash chromatographed (Merck silica gel) eluting with 1:1 ethyl acetate/hexane/1% acetic acid. The fractions containing clean desired product were combined, concentrated, azeotroped with ethyl acetate, and washed with water to remove the acetic acid. The organic layer was dried (sodium sulfate), filtered, and concentrated to give 3.22 g. of title compound as a white crystalline product; m.p. 166°-168° C.; [α]D =-146.8° (c=0.46, methylene chloride). TLC (1% acetic acid in 1:1 ethyl acetate/hexane) Rf =0.31.

Workup

  1. stirringthe resulting mixture was stirred for 3.0 hours
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed successively with 10% potassium bisulfate and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed (Merck silica gel)
  8. washeluting with 1:1 ethyl acetate/hexane/1% acetic acid
  9. additionThe fractions containing clean desired product
  10. concentrationconcentrated
  11. customazeotroped with ethyl acetate
  12. washwashed with water
  13. customto remove the acetic acid
  14. dry with materialThe organic layer was dried (sodium sulfate)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customto give 3.22 g

Sources & evidence

ORD record
ord-5ab7807d5d634430862fc49c96a5840a
Source dataset
uspto-grants-1996_06
Patent number
US05525723

Reaction notes

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