Hydrochloric Acid → benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyridin-2-ylsulfanylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1707447노트

반응식

HRID 1707447 반응식
C([S:4][CH2:5][S:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)(=O)C.C[O-].[Na+].CO.[C:18]1([CH:24]([O:31][C:32]([C:34]2[N:39]3[C:40](=[O:80])[C@@H:41]([NH:42][C:43](=[O:79])/[C:44](/[C:66]4[N:67]=[C:68]([NH:71][C:72]([O:74][C:75]([CH3:78])([CH3:77])[CH3:76])=[O:73])[S:69][CH:70]=4)=[N:45]\[O:46][C:47](C4C=CC=CC=4)([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C@H:38]3[S:37][CH2:36][C:35]=2OS(C)(=O)=O)=[O:33])C2C=CC=CC=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>CN(C)C=O.O1CCCC1.O>[C:18]1([CH:24]([O:31][C:32]([C:34]2[N:39]3[C:40](=[O:80])[C@@H:41]([NH:42][C:43](=[O:79])/[C:44](/[C:66]4[N:67]=[C:68]([NH:71][C:72]([O:74][C:75]([CH3:77])([CH3:76])[CH3:78])=[O:73])[S:69][CH:70]=4)=[N:45]\[O:46][C:47]([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)([C:48]4[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=4)[C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[C@H:38]3[S:37][CH2:36][C:35]=2[S:4][CH2:5][S:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)=[O:33])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 10260338benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 104653712-AcetylthiomethylthiopyridineHCID 23694274Sodium methanolate methanol

생성물 1

HCID 16143732benzhydryl (6R,7R)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyridin-2-ylsulfanylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate수율 145.8%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매2회HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

To a solution of 2-acetylthiomethylthiopyridine (249 mg: 1.25 mMol.) in a mixture of dimethylformamide (4 ml) and tetrahydrofuran (2 ml) cooling at -78° C. is added dropwise 1.26N-sodium methoxide-methanol solution (0.87 ml: 1.10 mMol.), and the mixture is stirred at -78° C. for 15 minutes. To this reaction mixture is added a solution of 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester (971 mg: 1.00 mMol.) in dimethylformamide (2 ml) and the mixture is stirred at -78° C. for 1 hour. The reaction mixture is mixed with 10% hydrochloric acid to stop the reaction, diluted with water, and extracted with ethyl acetate. The extract is washed with dilute aqueous sodium hydrogen carbonate and brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel chromatography (toluene: ethyl acetate=4:1) and silica gel rechromatography (toluene: ethyl acetate=7:1) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-(pyrid-2-ylthiomethylthio)-3-cephem-4-carboxylic acid diphenylmethyl ester as colorless foam (753 mg). Yield: 73%.

후처리

  1. stirringthe mixture is stirred at -78° C. for 1 hour
  2. customthe reaction
  3. extractionextracted with ethyl acetate
  4. washThe extract is washed with dilute aqueous sodium hydrogen carbonate and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography (toluene: ethyl acetate=4:1) and silica gel rechromatography (toluene: ethyl acetate=7:1)

출처 및 근거

ORD 기록
ord-28e6e66af4784d16969c27dd8bbd08da
출처 데이터셋
uspto-grants-1994_10
특허 번호
US05352792

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