Triethylamine → 6-(3-[Carbamoyl]-acrylamido)-2,2-dimethyl-3-(5-tetrazolyl)penam

HRID 1448378

반응식

HRID 1448378 반응식
[C:1]([OH:8])(=O)/[CH:2]=[CH:3]\[C:4]([NH2:6])=[O:5].C(N(CC)CC)C.ClC(OCC(C)C)=O.[NH2:24][CH:25]1[C:38](=[O:39])[N:27]2[CH:28]([C:33]3[NH:37][N:36]=[N:35][N:34]=3)[C:29]([CH3:32])([CH3:31])[S:30][C@H:26]12>CN1CCOCC1.O1CCCC1.O>[C:4]([CH:3]=[CH:2][C:1]([NH:24][CH:25]1[C:38](=[O:39])[N:27]2[CH:28]([C:33]3[NH:34][N:35]=[N:36][N:37]=3)[C:29]([CH3:31])([CH3:32])[S:30][C@H:26]12)=[O:8])(=[O:5])[NH2:6]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 5280451Maleamic acidHCID 178431949HCID 178431949, 화합물

생성물 1

HCID 1784319306-(3-[Carbamoyl]-acrylamido)-2,2-dimethyl-3-(5-tetrazolyl)penam수율 33%

시약·촉매·용매 3

HCID 79724-Methylmorpholine촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a stirred mixture of 1.15 g. (10 m mole) of maleamic acid and 1.40 ml. of triethylamine in 40 ml. of dry tetrahydrofuran, at 0° C., is added 1.57 ml (12 m mole) of isobutyl chloroformate followed by three drops of N-methylmorpholine. Stirring is continued for a further 30 minutes at 0° C. To this mixed anhydride is then added a solution prepared by adding 2.40 g. (10 m mole) of 6-amino-2,2-dimethyl-3-(5-tetrazolyl)penam to a mixture of 15 ml. of water and 15 ml. of tetrahydrofuran and adjusting the pH to 7.5. The resulting mixture is then stirred for a further 1 hour at 0° C. At this point, the tetrahydrofuran is removed by evaporation in vacuo, and the residue is diluted with more water. The pH is adjusted to 8.0 with 6 N sodium hydroxide, and then the mixture is extracted with ethyl acetate. The extracts are discarded. The pH of the residual aqueous phase is adjusted to 2.0 with 4 N hydrochloric acid and then the product is extracted into ethyl acetate. The organic layer is dried and concentrated in vacuo to give 6-(3-[carbamoyl]acrylamido)-2,2-dimethyl-3-(5-tetrazolyl)penam (1.03 g., 33% yield). The infrared spectrum (KBr disc) of the product shows absorption band at 1818 cm-1 (β-lactam) and 1692 cm-1. The NMR spectrum (DMSO-d6) shows bands at 7.00 and 6.25 (quartet, 2H, J=12 Hz, olefinic hydrogens), 5.80-5.48 ppm (multiplet, 2H, C-5 and C-6 hydrogens), 5.26 ppm (singlet, 1H, C-3 hydrogen), 1.65 ppm (singlet, 3H, C-2 methyl hydrogens) and 1.06 ppm (singlet, 3H, C-2 methyl hydrogens).

후처리

  1. additionTo a stirred mixture of 1.15 g
  2. customprepared
  3. additionby adding 2.40 g
  4. stirringThe resulting mixture is then stirred for a further 1 hour at 0° C
  5. customAt this point, the tetrahydrofuran is removed by evaporation in vacuo
  6. additionthe residue is diluted with more water
  7. extractionthe mixture is extracted with ethyl acetate
  8. extractionthe product is extracted into ethyl acetate
  9. customThe organic layer is dried
  10. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-5c7a812d1c4d410b8853bfd4aeebb3af
출처 데이터셋
uspto-grants-1979_12
특허 번호
US04179511

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