Reaktion #710416

Reaktionsgleichung

water

hydrochloric acid

Sodium hydroxide

(±)-7-[[2-[(Acetylthio)methyl]-1-oxo-3-phenylpropyl]amino]heptanoic acid, methyl ester

→

(±)-7-[[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]amino]heptanoic acid, methyl ester

Lösungsmittel

methanol

methanol

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturby warming
2. 2
   Temperaturchilled in an ice bath under nitrogen
3. 3
   workup.STIRRINGstirred for one hour
4. 4
   EinengenThe mixture is concentrated in vacuo
5. 5
   Sonstigeto remove all the methanol
6. 6
   workup.ADDITIONThe residue is diluted with water (20 ml.)
7. 7
   Extraktionextracted with ethyl acetate (3×15 ml.)
8. 8
   Waschenwashed with water and brine (15 ml
9. 9
   Trockneneach), dried (Na2SO4)
10. 10
    Einengenconcentrated
11. 11
    Sonstigeto yield 1.26 g
12. 12
    workup.DISSOLUTIONThis solid is dissolved in 25 ml
13. 13
    workup.STIRRINGthe mixture is stirred at room temperature for 30 minutes
14. 14
    FiltrationThe remaining zinc is filtered off
15. 15
    Einengenthe filtrate is concentrated in vacuo
16. 16
    Sonstigeto remove all the methanol
17. 17
    workup.ADDITIONThe residue is diluted with water (20 ml.)
18. 18
    Extraktionextracted with ethyl acetate (3×25 ml.)
19. 19
    Waschenwashed with 5% sodium bicarbonate, water and brine (2×20 ml
20. 20
    Trockneneach), dried (Na2SO4)
21. 21
    Einengenconcentrated
22. 22
    Sonstigeto yield 1.23 g
23. 23
    SonstigeThis material is purified by flash chromatography on 50 g
24. 24
    Waschenof Merck silica gel (230-400 mesh) eluting with ethyl acetate
25. 25
    Sonstigeto yield 980 mg
26. 26
    Filtrationfiltered through a cellulose microfilter
27. 27
    Einengenconcentrated in vacuo

Vorschrift

(±)-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.

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