Phosphorus oxychloride → 7-[2-Isopropoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid

HRID 1065916ノート

反応式

HRID 1065916 の反応式
P(Cl)(Cl)(Cl)=O.[CH:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([OH:14])=O)([CH3:8])[CH3:7].[NH2:23][CH:24]1[C:39](=[O:40])[N:26]2[C:27]([C:36]([OH:38])=[O:37])=[C:28]([CH2:31][O:32][C:33](=[O:35])[NH2:34])[CH2:29][S:30][C@H:25]12.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.CC(C)=O.CN(C)C=O>[CH:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([NH:23][CH:24]1[C:39](=[O:40])[N:26]2[C:27]([C:36]([OH:38])=[O:37])=[C:28]([CH2:31][O:32][C:33](=[O:35])[NH2:34])[CH2:29][S:30][C@H:25]12)=[O:14])([CH3:7])[CH3:8]

参加物

9

反応物 4

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 127847593-Carbamoyloxymethyl-7-amino-3-cephem-4-carboxylic acidHCID 538092752-(2-Formamidothiazol-4-yl)-2-isopropoxyiminoacetic acid

生成物 1

HCID 1317127307-[2-Isopropoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid収率 58.4%

試薬・触媒・溶媒 4

HCID 180Acetone溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒3 回

実験手順

Phosphorus oxychloride (0.92 g) was added dropwise over 3 minutes at -5° to -10° C. to a solution of dimethylformamide (0.44 g) in ethyl acetate (2 ml). Ethyl acetate (20 ml) was added thereto and after 10 minutes, 2-isopropoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetic acid (syn isomer) (1.29 g) was added thereto at -5° to -10° C. The mixture was stirred for 10 minutes to give a clear solution. On the other hand, 7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (1.37 g) was dissolved under stirring in a solution of sodium bicarbonate (1.68 g) in water (30 ml), and then acetone (20 ml) was added thereto. To the solution was added dropwise with stirring the ethyl acetate solution obtained above at 0° to 5° C. and at pH 6.5 to 7.5. After stirring for 20 minutes at the same temperature, the aqueous layer was separated and acetone was distilled off. The remaining aqueous layer was adjusted to pH 3.0 with 10% hydrochloric acid under ice-cooling and stirring. Precipitates were collected by filtration, washed with water and dried to give 7-[2-isopropoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (syn isomer) (1.5 g).

後処理

  1. customat -5° to -10° C
  2. customto give a clear solution
  3. additionTo the solution was added dropwise
  4. customobtained above at 0° to 5° C. and at pH 6.5 to 7.5
  5. stirringAfter stirring for 20 minutes at the same temperature
  6. customthe aqueous layer was separated
  7. distillationacetone was distilled off
  8. temperaturecooling
  9. stirringstirring
  10. customPrecipitates
  11. filtrationwere collected by filtration
  12. washwashed with water
  13. customdried

出典と根拠

ORDレコード
ord-6e6b9988f2c44c5e810d9a909ed31b4a
出典データセット
uspto-grants-1982_05
特許番号
US04331664

反応ノート

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