Hydrochloric Acid → (+/-)-7-[[2-(Mercaptomethyl)-1-oxo-3-phenylpropyl]amino]heptanoic acid, methyl ester

HRID 3758Notes

Reaction equation

HRID 3758 reaction equation
C([S:4][CH2:5][CH:6]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:7]([NH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])=[O:8])(=O)C.[OH-].[Na+].O.Cl>CO.[Zn]>[SH:4][CH2:5][CH:6]([CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:7]([NH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])=[O:8]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 14155012(+/-)-7-[[2-[(Acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]heptanoic acid, methyl ester

Product 1

HCID 14155013(+/-)-7-[[2-(Mercaptomethyl)-1-oxo-3-phenylpropyl]amino]heptanoic acid, methyl ester

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent3×

Procedure

(±)-7-[[2-[(Acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]heptanoic acid, methyl ester (1.43 g., 3.77 mmole) is dissolved in methanol (30 ml.) by warming, and then chilled in an ice bath under nitrogen. 1N Sodium hydroxide (3.77 ml., 1.0 eq.) is added dropwise over 10 minutes to this solution. The mixture is stirred at 0° for ten minutes and then allowed to warm to room temperature and stirred for one hour. The mixture is concentrated in vacuo to remove all the methanol. The residue is diluted with water (20 ml.) and extracted with ethyl acetate (3×15 ml.). These organic layers are combined, washed with water and brine (15 ml. each), dried (Na2SO4) and concentrated to yield 1.26 g. of a white solid. This solid is dissolved in 25 ml. of a 1:1 mixture of methanol: water and adjusted to pH of about 1.0 with concentrated hydrochloric acid. Zinc dust (80 mg.) is added to this solution and the mixture is stirred at room temperature for 30 minutes. The remaining zinc is filtered off and the filtrate is concentrated in vacuo to remove all the methanol. The residue is diluted with water (20 ml.) and then extracted with ethyl acetate (3×25 ml.). These organic layers are combined, washed with 5% sodium bicarbonate, water and brine (2×20 ml. each), dried (Na2SO4), and concentrated to yield 1.23 g. of a white solid. This material is purified by flash chromatography on 50 g. of Merck silica gel (230-400 mesh) eluting with ethyl acetate to yield 980 mg. of a white solid. This solid is taken up in methanol, filtered through a cellulose microfilter, and concentrated in vacuo to yield (±)-7-[[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]amino]heptanoic acid, methyl ester, m.p. 68°-70°. TLC (silica gel, benzene/acetic acid 4:1) Rf =0.44.

Workup

  1. temperatureby warming
  2. temperaturechilled in an ice bath under nitrogen
  3. stirringstirred for one hour
  4. concentrationThe mixture is concentrated in vacuo
  5. customto remove all the methanol
  6. additionThe residue is diluted with water (20 ml.)
  7. extractionextracted with ethyl acetate (3×15 ml.)
  8. washwashed with water and brine (15 ml
  9. dry with materialeach), dried (Na2SO4)
  10. concentrationconcentrated
  11. customto yield 1.26 g
  12. dissolutionThis solid is dissolved in 25 ml
  13. stirringthe mixture is stirred at room temperature for 30 minutes
  14. filtrationThe remaining zinc is filtered off
  15. concentrationthe filtrate is concentrated in vacuo
  16. customto remove all the methanol
  17. additionThe residue is diluted with water (20 ml.)
  18. extractionextracted with ethyl acetate (3×25 ml.)
  19. washwashed with 5% sodium bicarbonate, water and brine (2×20 ml
  20. dry with materialeach), dried (Na2SO4)
  21. concentrationconcentrated
  22. customto yield 1.23 g
  23. customThis material is purified by flash chromatography on 50 g
  24. washof Merck silica gel (230-400 mesh) eluting with ethyl acetate
  25. customto yield 980 mg
  26. filtrationfiltered through a cellulose microfilter
  27. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-878353b2e518459d97d4c3e89c51a6f3
Source dataset
uspto-grants-1988_02
Patent number
US04722810

Reaction notes

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