Phosphorus oxychloride → HCID 131716050、化合物

HRID 1074348ノート

反応式

HRID 1074348 の反応式
P(Cl)(Cl)(Cl)=O.[CH:6]1([O:9][N:10]=[C:11]([C:15]2[N:16]=[C:17]([NH:20][C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])[S:18][CH:19]=2)[C:12]([OH:14])=O)[CH2:8][CH2:7]1.[NH2:27][C@@H:28]1[C:45](=[O:46])[N:30]2[C:31]([C:42]([OH:44])=[O:43])=[C:32]([CH2:35][S:36][C:37]3[S:38][CH:39]=[N:40][N:41]=3)[CH2:33][S:34][C@H:29]12.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C)C=O>[CH:6]1([O:9][N:10]=[C:11]([C:15]2[N:16]=[C:17]([NH:20][C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])[S:18][CH:19]=2)[C:12]([NH:27][C@@H:28]2[C:45](=[O:46])[N:30]3[C:31]([C:42]([OH:44])=[O:43])=[C:32]([CH2:35][S:36][C:37]4[S:38][CH:39]=[N:40][N:41]=4)[CH2:33][S:34][C@H:29]23)=[O:14])[CH2:7][CH2:8]1

参加物

8

反応物 5

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 11708267BistrimethylsilylacetamidHCID 12889186(6R,7R)-7-Amino-8-oxo-3-[(1,3,4-thiadiazol-2-ylthio)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 53681275HCID 53681275、化合物

生成物 1

HCID 131716050HCID 131716050、化合物収率 95.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

Phosphorus oxychloride (0.24 ml) was dropwise added to a mixture of N,N-dimethylformamide (0.2 ml) and tetrahydrofuran (0.4 ml) under ice-cooling. After being stirred for 10 minutes at the same temperature, the mixture was cooled until a precipitate appeared. To the suspension was added 2-cyclopropyloxyimino-2-(2-trifluoroacetamidothiazol-4-yl) acetic acid (syn isomer) (647 mg) and additional tetrahydrofuran (4 ml). The mixture was stirred at the same temperature for 30 minutes to give an activated acid solution. On the other hand, a mixture of 7β-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (793 mg) and bis(trimethylsilyl)acetamide (2 ml) in tetrahydrofuran (20 ml) was stirred at 30° C. for 30 minutes to give a clear solution. To the clear solution was added the activated acid solution prepared above at -30° C. The mixture was stirred for 30 minutes at -20° C. to -15° C. The mixture was poured into ice-water, adjusted to pH 7.2 with saturated aqueous solution of sodium bicarbonate, and washed with ethyl acetate. The aqueous solution was adjusted to pH 2.5 with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diisopropyl ether to give 7β-[2-cyclopropyloxyimino-2-(2-trifluoroacetamidothiazol-4-yl)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.21 g) as a solid.

後処理

  1. temperaturecooling
  2. temperaturethe mixture was cooled until a precipitate
  3. stirringThe mixture was stirred at the same temperature for 30 minutes
  4. customto give an activated acid solution
  5. stirringwas stirred at 30° C. for 30 minutes
  6. customto give a clear solution
  7. additionTo the clear solution was added the activated acid solution
  8. customprepared above at -30° C
  9. stirringThe mixture was stirred for 30 minutes at -20° C. to -15° C
  10. washwashed with ethyl acetate
  11. extractionextracted with ethyl acetate
  12. washThe extract was washed with water
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated in vacuo
  15. customThe residue was triturated with diisopropyl ether

出典と根拠

ORDレコード
ord-9276c4cc3b574f9980ef61f99415d29f
出典データセット
uspto-grants-1990_11
特許番号
US04973699

反応ノート

読み込み中…