Phosphorus oxychloride → 7-[2-(2-Aminothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 434978ノート

反応式

HRID 434978 の反応式
P(Cl)(Cl)(Cl)=O.[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH2:18][C:19]#[CH:20])[C:13]([OH:15])=O)[N:11]=1.C[Si](CC(N)=O)(C)C.[NH2:29][CH:30]1[C:40](=[O:41])[N:32]2[C:33]([C:37]([OH:39])=[O:38])=[CH:34][CH2:35][S:36][C@H:31]12.C(=O)(O)[O-].[Na+]>O1CCCC1.O.CN(C)C=O>[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH2:18][C:19]#[CH:20])[C:13]([NH:29][CH:30]2[C:40](=[O:41])[N:32]3[C:33]([C:37]([OH:39])=[O:38])=[CH:34][CH2:35][S:36][C@H:31]23)=[O:15])[N:11]=1

参加物

9

反応物 5

HCID 24813Phosphorus oxychloride2 回HCID 357676Acetamide, 2-(trimethylsilyl)-2 回HCID 516892Sodium BicarbonateHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 543726822-(2-Aminothiazol-4-yl)-2-propargyloxyiminoacetic acid

生成物 1

HCID 1317124667-[2-(2-Aminothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-cephem-4-carboxylic acid収率 48.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Phosphoryl chloride (1.4 g.) was added dropwise to a suspension of 2-(2-aminothiazol-4-yl)-2-propargyloxyiminoacetic acid (syn isomer, 1.7 g.) in tetrahydrofuran (15 ml.) below 7° C., and stirred at the same temperature for 10 minutes. Phosphoryl chloride (1.4 g.), trimethylsilylacetamide (1.3 g.) and N,N-dimethylformamide (0.76 g.) were added to a solution, and stirred for 20 minutes to prepare the activated acid solution. On the other hand, trimethylsilylacetamide (7.8 g.) was added to a suspension of 7-amino-3-cephem-4-carboxylic acid (1.5 g.) in tetrahydrofuran (20 ml.), and stirred at 40° C. for 30 minutes. To the solution was added all at once the activated acid solution obtained above at -20° C., and stirred for 30 minutes at 0° C. After adding water (20 ml.) to the resultant solution at -20° C., the solution was adjusted to pH 7.5 with an aqueous solution of sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate and diisopropyl ether in turn, and treated with activated charcoal at pH 5.5. The solution was adjusted to pH 3.0, and the precipitates were collected by filtration and dried over phosphorus pentoxide under reduced pressure to give 7-[2-(2-aminothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 1.47 g.).

後処理

  1. stirringstirred for 20 minutes
  2. customto prepare the activated acid solution
  3. stirringstirred at 40° C. for 30 minutes
  4. additionTo the solution was added all at once the activated acid solution
  5. customobtained above at -20° C.
  6. stirringstirred for 30 minutes at 0° C
  7. customThe aqueous layer was separated
  8. washwashed with ethyl acetate and diisopropyl ether in turn
  9. additiontreated with activated charcoal at pH 5.5
  10. filtrationthe precipitates were collected by filtration
  11. dry with materialdried over phosphorus pentoxide under reduced pressure

出典と根拠

ORDレコード
ord-2bbfbdeff14048e7bf1e2c66dbf5f0b1
出典データセット
uspto-grants-1983_08
特許番号
US04399133

反応ノート

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