Phosphorus oxychloride → 7-[2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-methyl-3-cephem-4-carboxylic acid

HRID 255767노트

반응식

HRID 255767 반응식
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH2:16][O:17][CH:18]=[O:19])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.[NH2:25][CH:26]1[C:37](=[O:38])[N:28]2[C:29]([C:34]([OH:36])=[O:35])=[C:30]([CH3:33])[CH2:31][S:32][C@H:27]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH2:16][O:17][CH:18]=[O:19])[C:10]([NH:25][CH:26]2[C:37](=[O:38])[N:28]3[C:29]([C:34]([OH:36])=[O:35])=[C:30]([CH3:33])[CH2:31][S:32][C@H:27]23)=[O:12])[N:8]=1)=[O:2]

참가 물질

8

반응물 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 13475828(6R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 541333172-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetic acid

생성물 1

HCID 1317152957-[2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-methyl-3-cephem-4-carboxylic acid수율 46.5%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매2회

실험 절차

2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetic acid (syn isomer 2.9 g.), N,N-dimethylformamide (0.8 g.), phosphoryl chloride (1.7 g.) and dry ethyl acetate (23 ml.) were treated in a similar manner to that of the Example 1-(1) to give an activated acid solution. The solution was added to a solution of 7-amino-3-methyl-3-cephem-4-carboxylic acid (2.0 g.) and trimethylsilylacetamide (8.6 g.) in dry ethyl acetate (40 ml.) at -10° C. and stirred at the same temperature for an hour. After adding water (30 ml.) to the reaction mixture, the organic layer was separated and extracted with an aqueous solution of sodium bicarbonate (30 ml.). The extract was adjusted to pH 2.5 with conc. hydrochloric acid and extracted with ethyl acetate (50 ml.). The extract was washed with a saturated aqueous solution of sodium chloride, dried and evaporated in vacuo. The residue was triturated with diisopropyl ether to give 7-[2-(2-formamidothiazol- 4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-methyl-3-cephem-4-carboxylic acid (syn isomer, 2.10 g.).

후처리

  1. customto give an activated acid solution
  2. customthe organic layer was separated
  3. extractionextracted with an aqueous solution of sodium bicarbonate (30 ml.)
  4. extractionextracted with ethyl acetate (50 ml.)
  5. washThe extract was washed with a saturated aqueous solution of sodium chloride
  6. customdried
  7. customevaporated in vacuo
  8. customThe residue was triturated with diisopropyl ether

출처 및 근거

ORD 기록
ord-196657a7fe014c7aa62218d9283d953a
출처 데이터셋
uspto-grants-1987_10
특허 번호
US04698337

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