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Phosphorus pentachloride → (6R,7R)-7-[[(2Z)-2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]iminoacetyl]amino]-8-oxo-3-(3-oxobutanoyloxymethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 1088246
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HRID 1088246 반응식
[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][N:12]=[C:11](/[C:14](=[N:18]/[O:19][CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])/[C:15](O)=[O:16])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl.[NH2:34][C@@H:35]1[C:53](=[O:54])[N:37]2[C:38]([C:50]([OH:52])=[O:51])=[C:39]([CH2:42][O:43][C:44](=[O:49])[CH2:45][C:46](=[O:48])[CH3:47])[CH2:40][S:41][C@H:36]12>ClCCl>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][N:12]=[C:11](/[C:14](=[N:18]/[O:19][CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])/[C:15]([NH:34][C@@H:35]2[C:53](=[O:54])[N:37]3[C:38]([C:50]([OH:52])=[O:51])=[C:39]([CH2:42][O:43][C:44](=[O:49])[CH2:45][C:46](=[O:48])[CH3:47])[CH2:40][S:41][C@H:36]23)=[O:16])[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 3

HCID 24819Phosphorus pentachlorideHCID 117819897beta-Amino-3(3-oxobutyryloxymethyl)-3-cephem-4-carboxylic acidHCID 13604646(2Z)-2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]iminoacetic acid

생성물 1

HCID 88417246(6R,7R)-7-[[(2Z)-2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]iminoacetyl]amino]-8-oxo-3-(3-oxobutanoyloxymethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
수율 103.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 13 g of 2-(tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2(Z)-(tert-butoxycarbonylmethoxyimino)acetic acid in 100 ml of dichloromethane, 7 g of phosphorus pentachloride is added and the mixture is stirred for 20 minutes under ice-cooling. The reaction mixture is evaporated to dryness and to the residue is added hexane and the solvent is evaporated off again. The residue is dissolved in 5 ml of dichloromethane and the solution is added under ice-cooling to a solution prepared by allowing 10 g of 7β-amino-3-(3-oxobutyryloxymethyl)-3-cephem-4-carboxylic acid and 16 g of N,O-bistrimethylsilylacetamide to react in 200 ml of dichloromethane at room temperature for one hour. The mixture is stirred at the same temperature for one hour and the solvent is then evaporated under reduced pressure. The residue is dissolved in 300 ml of ethyl acetate and the solution is washed with water and then dried over anhydrous magnesium sulfate. Then, the solvent is evaporated off and the residue is triturated with hexane. Insoluble substance is collected by filtration to give 23 g of 7β-[2-(5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2(Z)-(tert-butoxycarbonylmethoxyimino)acetamido]-3-(3-oxobutyryloxymethyl)-3-cephem-4-carboxylic acid.

후처리

  1. temperaturecooling
  2. customThe reaction mixture is evaporated to dryness and to the residue
  3. additionis added hexane
  4. customthe solvent is evaporated off again
  5. dissolutionThe residue is dissolved in 5 ml of dichloromethane
  6. additionthe solution is added under ice-
  7. temperaturecooling to a solution
  8. customprepared
  9. stirringThe mixture is stirred at the same temperature for one hour
  10. customthe solvent is then evaporated under reduced pressure
  11. dissolutionThe residue is dissolved in 300 ml of ethyl acetate
  12. washthe solution is washed with water
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customThen, the solvent is evaporated off
  15. customthe residue is triturated with hexane
  16. filtrationInsoluble substance is collected by filtration

출처 및 근거

ORD 기록
ord-8f56c653778a42f9a7df3810cbb87021
출처 데이터셋
uspto-grants-1990_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04962100

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