4-Methylmorpholine → benzhydryl (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-carboxylate

HRID 1707436노트

반응식

HRID 1707436 반응식
Cl.[C:2]1([CH:8]([O:15][C:16]([C:18]2[N:23]3[C:24](=[O:27])[C@@H:25]([NH2:26])[C@H:22]3[S:21][CH2:20][C:19]=2[O:28][S:29]([CH3:32])(=[O:31])=[O:30])=[O:17])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:33]([O:37][C:38]([NH:40][C:41]1[S:42][CH:43]=[C:44](/[C:46](=[N:50]/[O:51][C:52]([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)/[C:47](O)=[O:48])[N:45]=1)=[O:39])([CH3:36])([CH3:35])[CH3:34].CN1CCOCC1.P(Cl)(Cl)(OC1C=CC=CC=1)=O>ClCCl.Cl.O>[C:2]1([CH:8]([O:15][C:16]([C:18]2[N:23]3[C:24](=[O:27])[C@@H:25]([NH:26][C:47](=[O:48])/[C:46](/[C:44]4[N:45]=[C:41]([NH:40][C:38]([O:37][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:39])[S:42][CH:43]=4)=[N:50]\[O:51][C:52]([C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=4)([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)[C:65]4[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=4)[C@H:22]3[S:21][CH2:20][C:19]=2[O:28][S:29]([CH3:32])(=[O:31])=[O:30])=[O:17])[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

8

반응물 4

HCID 79724-MethylmorpholineHCID 13038Phosphorodichloridic acid, phenyl esterHCID 10459636(Z)-2-(2-Boc-aminothiazole-4-yl-)-2-trityloxyiminoacetic acidHCID 883013187beta-Amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride

생성물 1

HCID 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-carboxylate수율 92%

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

To a suspension of 7β-amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride (37.27 g: 75 mMol.) and (Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetic acid (45.63 g; 86 mMol.) in dichloromethane (600 ml) is added at -30° C. N-methylmorpholine (27.2 ml: 0.25 Mol.) over 3 minutes. After 4 minutes, phenyl dichlorophosphate (12.3 ml: 82 mMol.) is added to the mixture. After stirring over 3 hours, the mixture is diluted with 10% hydrochloric acid (40 ml) and water and extracted with ethyl acetate. The extract is washed with water, aqueous sodium hydrogen carbonate, dilute hydrochloric acid, and water, dried over sodium sulfate, and concentrated under reduced pressure. The residue is dissolved in isopropanol (2 liters) by warming and cooled to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-trityloxyiminoacetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester (67 g). Colorless powder. Yield: 92%.

후처리

  1. additionis added at -30° C
  2. extractionextracted with ethyl acetate
  3. washThe extract is washed with water, aqueous sodium hydrogen carbonate, dilute hydrochloric acid, and water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue is dissolved in isopropanol (2 liters)
  7. temperatureby warming
  8. temperaturecooled

출처 및 근거

ORD 기록
ord-2508a4b70fab40288141c5d22c12d300
출처 데이터셋
uspto-grants-1994_10
특허 번호
US05352792

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