4-Methylmorpholine → 7beta-[2-(5-Tert.-butyloxycarbonylaminomethyl-2-thienyl)-acetylamino]-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid

HRID 2398516

반응식

HRID 2398516 반응식
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:14][C:13]([CH2:15][C:16]([OH:18])=O)=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[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][S:43][C:44]3[S:45][C:46]([CH3:49])=[N:47][N:48]=3)[CH2:40][S:41][C@H:36]12>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[S:14][C:13]([CH2:15][C:16]([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][S:43][C:44]4[S:45][C:46]([CH3:49])=[N:47][N:48]=4)[CH2:40][S:41][C@H:36]23)=[O:18])=[CH:12][CH:11]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

6

반응물 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 6350581Cefazolin deacylatedHCID 202932812-[5-({[(Tert-butoxy)carbonyl]amino}methyl)thiophen-2-yl]aceticacid

생성물 1

HCID 705965757beta-[2-(5-Tert.-butyloxycarbonylaminomethyl-2-thienyl)-acetylamino]-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

The starting material is prepared as follows: A solution of 4.08 g of 2-(5-tert.-butyloxycarbonylaminomethyl-2-thienyl)-acetic acid in 200ml of methylene chloride containing 1.65 ml of 4-methyl-morpholine is cooled to -20° under exclusion of moisture and treated dropwise with 1.95 ml of chloroformic acid isobutyl ester. After 30 minutes a solution of 5.16 g of 7β-amino-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid and 7.20 ml N,O-bis-(trimethylsilyl)-acetic acid amide in 150 ml of methylene chloride is added, whereupon the reaction mixture is stirred during one hour at -20° and during four hours while the temperature is allowed to slowly rise to room temperature and is then evaporated under reduced pressure. The residue is dissolved in water with the addition of sodium hydrogen carbonate until the pH reaches 8. The solution is washed with ethyl acetate, the separated aqueous layer is acidified to pH 2 with aqueous phosphoric acid of 20% strength and is extracted with ethyl acetate. The organic extract is washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated under reduced pressure. One thus obtains the 7β-[2-(5-tert.-butyloxycarbonylaminomethyl-2-thienyl)-acetylamino]-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid; thin layer chromatogram (silicagel): Rf = 0,40 (system: n-butanol/acetic acid/water45:45:10), ultraviolet absorption spectrum (ethanol): λmax 244 mμ (ε = 16900); infrared absorption spectrum (in mineral oil): characteristic bonds at 2,93 μ, 5,60 μ, 5,90 μ, and 6.55 μ.

후처리

  1. customThe starting material is prepared
  2. customto slowly rise to room temperature
  3. customis then evaporated under reduced pressure
  4. dissolutionThe residue is dissolved in water with the addition of sodium hydrogen carbonate until the pH
  5. washThe solution is washed with ethyl acetate
  6. extractionis extracted with ethyl acetate
  7. extractionThe organic extract
  8. washis washed with a saturated aqueous sodium chloride solution
  9. dry with materialdried over magnesium sulfate
  10. customevaporated under reduced pressure

출처 및 근거

ORD 기록
ord-e3e2f5bbfdd34b09b22fadd690b63695
출처 데이터셋
uspto-grants-1977_05
특허 번호
US04024249

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