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

HRID 1322

反応式

HRID 1322 の反応式
[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]

参加物

8

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 74236Tetrabutylammonium Bromide触媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒2 回HCID 24083Sulfuric acid magnesium salt (1:1)溶媒

実験手順

A solution of (3R-cis)-tetrahydro-3-phenyl-6-[[(phenylmethoxy)carbonyl]amino]-1,4-thiazepine-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).

後処理

  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

出典と根拠

ORDレコード
ord-d33b6c72571d4550bdc29dc44648e499
出典データセット
uspto-grants-1998_03
特許番号
US05723602

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