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

HRID 2256439

반응식

HRID 2256439 반응식
[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]

참가 물질

8

반응물 3

HCID 7748Ethyl bromoacetate2회HCID 14797Potassium HydroxideHCID 13877918(3R-cis)-tetrahydro-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepin-5(4H)-one

생성물 1

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

시약·촉매·용매 4

HCID 74236Tetrabutylammonium Bromide촉매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매2회HCID 24083Sulfuric acid magnesium salt (1:1)용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-263d2860ae974f21bc2e5433d9fb7594
출처 데이터셋
uspto-grants-1997_08
특허 번호
US05654294

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