Phosphorus oxychloride → 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 615761노트

반응식

HRID 615761 반응식
[O:1]1[C:6]([C:7](=[N:11][O:12][CH2:13][CH2:14][CH3:15])[C:8]([OH:10])=O)=[CH:5][S:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.[NH2:21][CH:22]1[C:40](=[O:41])[N:24]2[C:25]([C:37]([OH:39])=[O:38])=[C:26]([CH2:29][S:30][C:31]3[N:35]([CH3:36])[N:34]=[N:33][N:32]=3)[CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C>O.C(OCC)(=O)C.CN(C)C=O>[O:1]1[C:6]([C:7](=[N:11][O:12][CH2:13][CH2:14][CH3:15])[C:8]([NH:21][CH:22]2[C:40](=[O:41])[N:24]3[C:25]([C:37]([OH:39])=[O:38])=[C:26]([CH2:29][S:30][C:31]4[N:35]([CH3:36])[N:34]=[N:33][N:32]=4)[CH2:27][S:28][C@H:23]23)=[O:10])=[CH:5][S:4][CH2:3][CH2:2]1

참가 물질

8

반응물 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 537836602-(2,3-Dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid

생성물 1

HCID 1317120127-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid수율 83.4%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매2회

반응 조건

온도
40 °C

실험 절차

2-(2,3-Dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid (syn isomer, 1.55 g.), dry N,N-dimethylformamide (0.56 ml.), dry ethyl acetate (2.1 ml.) and phosphoryl chloride (0.66 ml.) were treated in a conventional manner to give an activated acid solution. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (2 g.) and trimethylsilylacetamide (5.6 g.) were added to dry ethyl acetate (40 ml.) and stirred at 40° C. for an hour. To the solution was added the activated acid solution at -15° C. and stirred at -10° to -20° C. for 2 hours. Water (50 ml.) was added to the resultant solution and the ethyl acetate layer was separated. Water (30 ml.) was added to the ethyl acetate layer and adjusted to pH 7.5 with sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate and adjusted to pH 2.0 with 10% hydrochloric acid. The precipitates were collected by filtration, washed with water and dried over phosphorus pentoxide under reduced pressure to give 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2.75 g.).

후처리

  1. customto give an activated acid solution
  2. additionTo the solution was added the activated acid solution at -15° C.
  3. stirringstirred at -10° to -20° C. for 2 hours
  4. customthe ethyl acetate layer was separated
  5. additionWater (30 ml.) was added to the ethyl acetate layer and adjusted to pH 7.5 with sodium bicarbonate
  6. customThe aqueous layer was separated
  7. washwashed with ethyl acetate
  8. filtrationThe precipitates were collected by filtration
  9. washwashed with water
  10. dry with materialdried over phosphorus pentoxide under reduced pressure

출처 및 근거

ORD 기록
ord-5f13475263974093b67689c56a5a82b6
출처 데이터셋
uspto-grants-1985_02
특허 번호
US04500709

반응 노트

불러오는 중…