Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate

HRID 435335

반응식

HRID 435335 반응식
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]#[CH:17])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[NH2:43][CH:44]1[C:65](=[O:66])[N:46]2[C:47]([C:52]([O:54][CH2:55][C:56]3[CH:61]=[CH:60][C:59]([N+:62]([O-:64])=[O:63])=[CH:58][CH:57]=3)=[O:53])=[C:48]([OH:51])[CH2:49][S:50][C@H:45]12>C(OCC)(=O)C.O.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]#[CH:17])[C:10]([NH:43][CH:44]2[C:65](=[O:66])[N:46]3[C:47]([C:52]([O:54][CH2:55][C:56]4[CH:57]=[CH:58][C:59]([N+:62]([O-:64])=[O:63])=[CH:60][CH:61]=4)=[O:53])=[C:48]([OH:51])[CH2:49][S:50][C@H:45]23)=[O:12])[N:8]=1)=[O:2]

참가 물질

9

반응물 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 537194582-(2-Formamidothiazol-4-yl)-2-(propargyloxyimino)acetic acidHCID 681232354-Nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate

생성물 1

HCID 1317130574-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate수율 60.6%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매3회

실험 절차

2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetic acid (syn isomer, 0.506 g.), N,N-dimethylformamide (0.161 g.), phosphoryl chloride (0.337 g.) and ethyl acetate (7.9 ml.) were treated in a similar manner to that of Example 15-(1) to give the activated acid solution. On the other hand, trimethylsilylacetamide (1.85 g.) and bis(trimethylsilyl)acetamide (1.60 g.) were added to a suspension of 4-nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate (0.703 g.) in ethyl acetate (10 ml.) and stirred at room temperature for an hour. To the solution was added the activated acid solution obtained above at -10° C. all at once, and stirred at the same temperature for an hour. Water (20 ml.) and ethyl acetate (20 ml.) were added to the solution. The organic layer was separated, washed with a saturated aqueous solution of sodium bicarbonate (8 ml.) and an aqueous solution of sodium chloride (15 ml.), and dried over magnesium sulfate. After the solution was concentrated in vacuo, the residue was pulverized with diethyl ether and the precipitates were collected by filtration to give 4-nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate (syn isomer, 0.71 g.).

후처리

  1. customto give the activated acid solution
  2. additionTo the solution was added the activated acid solution
  3. customobtained above at -10° C. all at once, and
  4. stirringstirred at the same temperature for an hour
  5. customThe organic layer was separated
  6. washwashed with a saturated aqueous solution of sodium bicarbonate (8 ml.)
  7. dry with materialan aqueous solution of sodium chloride (15 ml.), and dried over magnesium sulfate
  8. concentrationAfter the solution was concentrated in vacuo
  9. filtrationthe precipitates were collected by filtration

출처 및 근거

ORD 기록
ord-a8e5e36111cd49a6b57085372c25ff08
출처 데이터셋
uspto-grants-1983_08
특허 번호
US04400379

연결된 노트

불러오는 중…