Ethyl bromoacetate → (3R-cis)-Tetrahydro-5-oxo-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepine-4(5H)-acetic acid, ethyl ester

HRID 343040

Reaktionsgleichung

Reaktionsgleichung von HRID 343040
[C:1]1([C@H:7]2[NH:13][C:12](=[O:14])[C@@H:11]([NH:15][C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:10][S:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>O1CCCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.S([O-])([O-])(=O)=O.[Mg+2]>[O:14]=[C:12]1[C@@H:11]([NH:15][C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[CH2:10][S:9][CH2:8][C@@H:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:13]1[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]

Komponenten

8

Edukt 3

HCID 7748Ethyl bromoacetate2×HCID 14797Potassium HydroxideHCID 13877918(3R-cis)-tetrahydro-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepin-5(4H)-one

Produkt 1

HCID 86751054(3R-cis)-Tetrahydro-5-oxo-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepine-4(5H)-acetic acid, ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 74236Tetrabutylammonium BromideKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×HCID 24083Sulfuric acid magnesium salt (1:1)Lösungsmittel

Versuchsvorschrift

A solution of (3R-cis)-tetrahydro-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepin-5(4H)-one (1.16 g., 3.25 mmol) [prepared as described by Yanagisawa et al., J. Med. Chem., Vol. 30, p. 1984-1991 (1987)] in distilled tetrahydrofuran (30 ml.), under an atmosphere of argon, was cooled to 0° C. and treated with powdered potassium hydroxide (540 mg., 10 mmol) and tetrabutylammonium bromide (97 mg, 0.3 mmol). Ethyl bromoacetate (501 mg., 3 mmol) was added dropwise with stirring. The mixture was stirred cold for two hours and then additional ethyl bromoacetate (501 mg., 3 mmol) was added. The mixture was stirred cold for an additional two hours and then diluted with ethyl acetate (50 ml) and anhydrous magnesium sulfate was added. The reaction mixture was filtered through a magnesium sulfate pad and the pad was washed several times with ethyl acetate. The filtrate was poured into cold 1N hydrochloric acid solution (40 ml) and the layers were separated. The organic layer was dried (magnesium sulfate), filtered and freed of solvent in vacuo leaving an oil which was purified by chromatography on silica gel, eluting with 10-30% ethyl acetate in hexane to give 730 mg. of product; Rf =0.32 (ethyl acetate:hexanes, 1:2).

Aufarbeitung

  1. stirringThe mixture was stirred cold for two hours
  2. stirringThe mixture was stirred cold for an additional two hours
  3. additionwas added
  4. filtrationThe reaction mixture was filtered through a magnesium sulfate pad
  5. washthe pad was washed several times with ethyl acetate
  6. additionThe filtrate was poured into cold 1N hydrochloric acid solution (40 ml)
  7. customthe layers were separated
  8. dry with materialThe organic layer was dried (magnesium sulfate)
  9. filtrationfiltered
  10. customleaving an oil which
  11. customwas purified by chromatography on silica gel
  12. washeluting with 10-30% ethyl acetate in hexane
  13. customto give 730 mg

Quellen und Nachweise

ORD-Eintrag
ord-386ad5746959486e99457b7bd2ce0402
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859239

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