Trifluoroacetic acid → (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(pyridin-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 992697노트

반응식

HRID 992697 반응식
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:44]/[O:45]C(=O)C)/[C:8]([NH:10][C@@H:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([O:28]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:27])=[C:15]([S:18][CH2:19][C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.FC(F)(F)C(O)=O>ClCCl.C1(OC)C=CC=CC=1>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:44]/[OH:45])/[C:8]([NH:10][C@@H:11]2[C:42](=[O:43])[N:13]3[C:14]([C:26]([OH:28])=[O:27])=[C:15]([S:18][CH2:19][C:20]4[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1

참가 물질

5

반응물 2

HCID 6422Trifluoroacetic acidHCID 88178984benzhydryl (6R,7R)-7-[[(2Z)-2-acetyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-8-oxo-3-(pyridin-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

생성물 1

HCID 10458367(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(pyridin-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid수율 17.7%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 7519Anisole용매

실험 절차

To a suspension of diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetamido]-3-[(4-pyridyl)methylthio]-3-cephem-4-carboxylate (2.37 g, 3.51 m mol) in a mixture of dichloromethane (12 ml) and anisole (2.4 ml) was added trifluoroacetic acid (4.8 ml) at 5° C. and the mixture was stirred at the same temperature for 2 hours. The mixture was poured into IPE (300 ml) and the precipitates were collected by filtration, washed with IPE and dried in vacuo. The powder was suspended in a mixture of water (150 ml) and methanol (7.5 ml), and ammonium chloride (563 mg, 10.5 m mol) was added thereto. The mixture was stirred at room temperature with keeping the pH to 8 by addition of saturated NaHCO3 aqueous solution. The mixture was adjusted to pH ca. 6 by addition of 6N HCl and by evaporated in vacuo. The residue was adjusted to pH 3.5 by addition of 6N HCl and chromatographed on HP-20 (80 ml) and eluted with 5% aqueous IPA. The eluent was lyophilized and the crude product was purified by preparative HPLC to give 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-[(4-pyridyl)methylthio]-3-cephem-4-carboxylic acid (295 mg).

후처리

  1. additionThe mixture was poured into IPE (300 ml)
  2. filtrationthe precipitates were collected by filtration
  3. washwashed with IPE
  4. customdried in vacuo
  5. additionThe powder was suspended in a mixture of water (150 ml) and methanol (7.5 ml), and ammonium chloride (563 mg, 10.5 m mol)
  6. additionwas added
  7. stirringThe mixture was stirred at room temperature
  8. additionby addition of saturated NaHCO3 aqueous solution
  9. additionThe mixture was adjusted to pH ca. 6 by addition of 6N HCl
  10. customby evaporated in vacuo
  11. additionThe residue was adjusted to pH 3.5 by addition of 6N HCl
  12. customchromatographed on HP-20 (80 ml)
  13. washeluted with 5% aqueous IPA
  14. customthe crude product was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-3d043b000dd841be9770cc7aec33f688
출처 데이터셋
uspto-grants-2002_10
특허 번호
US06468995B1

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