Hydrochloric Acid → HCID 53895358, compound

HRID 363514Notes

Reaction equation

HRID 363514 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:28]([O:30]CC)=[O:29])[CH2:10][C:11]1[S:12][C:13]([NH:16][C:17]([NH:19]C(=O)C2C=CC=CC=2)=[S:18])=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.C(OCC)(=O)C>O1CCCC1>[C:1]([O:5][C:6]([NH:8][CH:9]([C:28]([OH:30])=[O:29])[CH2:10][C:11]1[S:12][C:13]([NH:16][C:17]([NH2:19])=[S:18])=[CH:14][CH:15]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 54558117HCID 54558117, compound

Product 1

HCID 53895358HCID 53895358, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of Ethyl N-(tert-butoxycarbonyl)-3-(5-(3-benzoylthioureido)-2-thienyl)-DL-alaninate (4.90 g, 10.2 mmol) in tetrahydrofuran (100 ml) was added 2N aqueous sodium hydroxide (12 ml, 24.0 mmol). The mixture was heated to reflux for 2.5 hours and cooled to room temperature. The mixture was placed in an ice bath and carefully neutralized to approximately pH7 with concentrated hydrochloric acid. The solvent was removed at reduced pressure to a volume of approximately 20-25 ml of a dark aqueous solution, and was extracted four times with ethyl acetate. The aqueous layer was adjusted to approximately pH4 with concentrated hydrochloric acid and concentrated at reduced pressure to give a dark red gummy solid. This material was taken up into ethyl acetate. All of the combined organic layers were dried over magnesium sulphate and the solvent was removed at reduced pressure to give a dark red gummy oil. This material was purified by column chromatography on silica gel eluting with 7.5:92.5:0.5 methanol:dichloromethane: acetic acid. The fractions containing the desired product were combined and concentrated at reduced pressure. The residue was redissolved in a small amount of methanol, diluted with toluene and reconcentrated at reduced pressure to azeotropically remove any remaining acetic acid. This process was repeated three times. N-(Tert-butoxycarbonyl)-3-(5-thioureido-2-thienyl)-DL-alanine. (2.33 g, 66%) was obtained as a yellow solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2.5 hours
  3. customThe mixture was placed in an ice bath
  4. customThe solvent was removed at reduced pressure to a volume of approximately 20-25 ml of a dark aqueous solution
  5. extractionwas extracted four times with ethyl acetate
  6. concentrationconcentrated at reduced pressure
  7. customto give a dark red gummy solid
  8. dry with materialAll of the combined organic layers were dried over magnesium sulphate
  9. customthe solvent was removed at reduced pressure
  10. customto give a dark red gummy oil
  11. customThis material was purified by column chromatography on silica gel eluting with 7.5:92.5:0.5 methanol
  12. additionThe fractions containing the desired product
  13. concentrationconcentrated at reduced pressure
  14. dissolutionThe residue was redissolved in a small amount of methanol
  15. additiondiluted with toluene
  16. customto azeotropically remove any remaining acetic acid
  17. custom(2.33 g, 66%) was obtained as a yellow solid

Sources & evidence

ORD record
ord-90d40d9e5ff14cbcb05a69de99c9cba2
Source dataset
uspto-grants-1999_02
Patent number
US05874472

Reaction notes

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