Oxalyl chloride → (+/-)-4-[[2-[(Acetylthio)methyl]-1 oxo-3-phenylpropyl]amino]butanoic acid, methyl ester

HRID 3756

反応式

HRID 3756 の反応式
C(Cl)(=O)C(Cl)=O.[C:7]([S:10][CH2:11][CH:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:13]([OH:15])=O)(=[O:9])[CH3:8].Cl.[NH2:24][CH2:25][CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29].C(N(C(C)C)CC)(C)C>C(OCC)C.CN(C)C=O.C(Cl)Cl>[C:7]([S:10][CH2:11][CH:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:13]([NH:24][CH2:25][CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])=[O:15])(=[O:9])[CH3:8]

参加物

8

反応物 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 27563834-Aminobutyric acid methyl ester hydrochlorideHCID 99917962-[(Acetylthio)methyl]-3-phenylpropionic Acid

生成物 1

HCID 13477463(+/-)-4-[[2-[(Acetylthio)methyl]-1 oxo-3-phenylpropyl]amino]butanoic acid, methyl ester

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

実験手順

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°.

後処理

  1. concentrationAfter concentrating in vacuo
  2. additionthe residue is treated with tetrahydrofuran (10 ml.)
  3. concentrationagain concentrated
  4. customto remove excess oxalyl chloride
  5. additionThe resulting residue is treated with methylene chloride (5 ml.)
  6. customthe soluble portion is transferred to a dropping funnel
  7. additionThis soluton is added, dropwise over 10 minutes, to a cold (-5°)
  8. stirringAfter stirring for 3 hours in the cold, the yellow solution
  9. concentrationis concentrated in vacuo
  10. additionThe residue is treated with ethyl acetate (60 ml.)
  11. filtrationfiltered
  12. customto remove diisopropylethylamine hydrochloride
  13. washwashed sequentially with 10% potassium bisulfate, water, 50% saturated sodium bicarbonate, and 50% brine (30 ml
  14. dry with materialThe organic layer is dried (Na2SO4)
  15. concentrationconcentrated to a light brown solid (1.34 g.)
  16. customdried
  17. washElution with 5:2 hexane/acetone
  18. customyields 1.09 g

出典と根拠

ORDレコード
ord-f14fe96832c846f8acc6375afbb7a901
出典データセット
uspto-grants-1988_02
特許番号
US04722810

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