Phosphorisocyanatidic dichloride → Cefuroxime

HRID 894834

反応式

HRID 894834 の反応式
ClP([N:5]=[C:6]=[O:7])(Cl)=O.[O:8]1[CH:12]=[CH:11][CH:10]=[C:9]1/[C:13](=[N:31]/[O:32][CH3:33])/[C:14]([NH:16][C@@H:17]1[C:29](=[O:30])[N:19]2[C:20]([C:26]([OH:28])=[O:27])=[C:21]([CH2:24][OH:25])[CH2:22][S:23][C@H:18]12)=[O:15].C([O-])(=O)C.[Na+]>C1COCC1.O>[CH3:33][O:32]/[N:31]=[C:13](\[C:14]([NH:16][C@@H:17]1[C:29](=[O:30])[N:19]2[C:20]([C:26]([OH:28])=[O:27])=[C:21]([CH2:24][O:25][C:6]([NH2:5])=[O:7])[CH2:22][S:23][C@H:18]12)=[O:15])/[C:9]1[O:8][CH:12]=[CH:11][CH:10]=1

参加物

6

反応物 3

HCID 70090Phosphorisocyanatidic dichlorideHCID 517045Sodium Acetate2 回HCID 9800056(6R,7R)-7-(((2Z)-2-(2-Furanyl)-2-(methoxyimino)acetyl)amino)-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid

生成物 1

HCID 5479529Cefuroxime

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Dichlorophosphinyl isocyanate (1.46 ml,) was added to a solution of (6R,7R)-7-[Z-2-(fur-2-yl)-2-methoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid (3.81 g) in THF (50 ml) at 22°, the temperature rising to 31°. The reaction mixture was stirred for 15 minutes and then added to a solution of sodium acetate (5.72 g) in water (50 ml). More sodium acetate (1.64 g) was added over 10 minutes to give a stable pH of 4.6. This solution was stirred at 30° for 1 hour and then heated at 45° for 3.5 hours when TLC (as Example 3) showed the reaction to be complete. The solution, pH 4.6, was clarified by filtration, adjusted to pH 7.0 with aqueous NaHCO3 solution and washed twice with ethyl acetate. The aqueous phase was stirred and acidified to pH 1.9 with dilute hydrochloric acid to precipitate the title compound (2.80 g, 66.0%); purity by HPLC 95.8% and by TLC 96%.

後処理

  1. customrising to 31°
  2. customto give a stable pH of 4.6
  3. stirringThis solution was stirred at 30° for 1 hour
  4. temperatureheated at 45° for 3.5 hours when TLC (as Example 3)
  5. customthe reaction
  6. filtrationThe solution, pH 4.6, was clarified by filtration
  7. washwashed twice with ethyl acetate
  8. stirringThe aqueous phase was stirred
  9. customto precipitate the title compound (2.80 g, 66.0%)

出典と根拠

ORDレコード
ord-b7a20f3b370d49f79a0e20fdd05b1b08
出典データセット
uspto-grants-1981_08
特許番号
US04284767

関連ノート

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