Reaktion #3852

Reaktionsgleichung

Oxalyl chloride

(±)-2-[(acetylthio)methyl]-3-phenylpropanoic acid

4-aminobutanoic acid, methyl ester, hydrochloride

diisopropylethylamine

→

(±)-4-[[2-[(Acetylthio)methyl]-1 oxo-3-phenylpropyl]amino]butanoic acid, methyl ester

Lösungsmittel

ethyl ether

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenAfter concentrating in vacuo
2. 2
   workup.ADDITIONthe residue is treated with tetrahydrofuran (10 ml.)
3. 3
   Einengenagain concentrated
4. 4
   Sonstigeto remove excess oxalyl chloride
5. 5
   workup.ADDITIONThe resulting residue is treated with methylene chloride (5 ml.)
6. 6
   Sonstigethe soluble portion is transferred to a dropping funnel
7. 7
   workup.ADDITIONThis soluton is added, dropwise over 10 minutes, to a cold (-5°)
8. 8
   workup.STIRRINGAfter stirring for 3 hours in the cold, the yellow solution
9. 9
   Einengenis concentrated in vacuo
10. 10
    workup.ADDITIONThe residue is treated with ethyl acetate (60 ml.)
11. 11
    Filtrationfiltered
12. 12
    Sonstigeto remove diisopropylethylamine hydrochloride
13. 13
    Waschenwashed sequentially with 10% potassium bisulfate, water, 50% saturated sodium bicarbonate, and 50% brine (30 ml
14. 14
    TrocknenThe organic layer is dried (Na2SO4)
15. 15
    Einengenconcentrated to a light brown solid (1.34 g.)
16. 16
    Sonstigedried
17. 17
    WaschenElution with 5:2 hexane/acetone
18. 18
    Sonstigeyields 1.09 g

Vorschrift

Oxalyl chloride (0.37 ml., 4.2 mmole) is added, under nitrogen, to a solution of (±)-2-[(acetylthio)methyl]-3-phenylpropanoic acid (0.95 g., 4.0 mmole) in ethyl ether (8 ml.). This mixture is cautiously treated with a catalytic amont of dimethylformamide (3 drops), and then stirred for one hour at room temperature. After concentrating in vacuo, the residue is treated with tetrahydrofuran (10 ml.) and again concentrated to remove excess oxalyl chloride. The resulting residue is treated with methylene chloride (5 ml.), and the soluble portion is transferred to a dropping funnel. This soluton is added, dropwise over 10 minutes, to a cold (-5°), stirred solution of 4-aminobutanoic acid, methyl ester, hydrochloride (0.68 g., 4.4 mmole) and diisopropylethylamine (1.6 ml., 9.0 mmole) in methylene chloride (10 ml.) under nitrogen. After stirring for 3 hours in the cold, the yellow solution is concentrated in vacuo. The residue is treated with ethyl acetate (60 ml.), filtered to remove diisopropylethylamine hydrochloride, and washed sequentially with 10% potassium bisulfate, water, 50% saturated sodium bicarbonate, and 50% brine (30 ml. each). The organic layer is dried (Na2SO4) and concentrated to a light brown solid (1.34 g.). This solid is adsorbed onto a small amount of silica gel (230- 400 mesh), dried, and applied to column of 80 g. of the same silica. Elution with 5:2 hexane/acetone yields 1.09 g. of (±)-4-[[2-[(acetylthio)methyl-1-oxo-3-phenylpropyl]amino]butanoic acid, methyl ester as a white solid; m.p. 81°-82°.

Quelle