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Hydrochloric Acid → 7-[2-(2-formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 255769
ノート
印刷プレビュー

反応式

HRID 255769 の反応式
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][C:21](=O)[NH2:22])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[NH2:24][CH:25]1[C:43](=[O:44])[N:27]2[C:28]([C:40]([OH:42])=[O:41])=[C:29]([CH2:32][S:33][C:34]3[N:38]([CH3:39])[N:37]=[N:36][N:35]=3)[CH2:30][S:31][C@H:26]12.Cl>O1CCCC1.CC(C)=O.C(OCC)(=O)C.C(N(CC)CC)C.CN(C)C=O>[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][C:21]#[N:22])[C:15]([NH:24][CH:25]2[C:43](=[O:44])[N:27]3[C:28]([C:40]([OH:42])=[O:41])=[C:29]([CH2:32][S:33][C:34]4[N:38]([CH3:39])[N:37]=[N:36][N:35]=4)[CH2:30][S:31][C@H:26]23)=[O:17])[N:13]=1)=[O:7]
参加物実験手順後処理出典と根拠反応ノート

参加物

10

反応物 4

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 538052302-(2-Formamidothiazol-4-yl)-2-carbamoylmethoxyiminoacetic acid

生成物 1

HCID 1317152977-[2-(2-formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid
収率 51.1%

試薬・触媒・溶媒 5

HCID 180Acetone溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8471Triethylamine溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of phosphoryl chloride (3.68 g.), N,N-dimethylformamide (1.75 g.) and tetrahydrofuran (4 ml.) was stirred at -5° to -10° C. for 30 minutes and added to a suspension of 2-(2-formamidothiazol-4-yl)-2-carbamoylmethoxyiminoacetic acid (syn isomer, 2 g.) in tetrahydrofuran (16 ml.). The mixture was stirred at the same temperature to give an activated acid solution. On the other hand, a suspension of 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (3.62 g.) in 50% aqueous acetone (36 ml.) was adjusted to pH 7.5 with triethylamine. The activated acid solution was added dropwise to the above solution at 0° to -5° C. while keeping at pH 7.5 to 8.0 with triethylamine and stirred at the same temperature for 30 minutes. Ethyl acetate (100 ml.) was added to the resultant solution and adjusted to pH 2.5 with 10% hydrochloric acid. After filtration, the filtrate was extracted with ethyl acetate (100 ml.) twice. The extracts were washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diethyl ether and the precipitates were collected by filtration to give 7-[2-(2-formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2.12 g.).

後処理

  1. customto give an activated acid solution
  2. additionThe activated acid solution was added dropwise to the above solution at 0° to -5° C.
  3. stirringstirred at the same temperature for 30 minutes
  4. filtrationAfter filtration
  5. extractionthe filtrate was extracted with ethyl acetate (100 ml.) twice
  6. washThe extracts were washed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was triturated with diethyl ether
  10. filtrationthe precipitates were collected by filtration

出典と根拠

ORDレコード
ord-f6192a7925494e8590638fcf7d5e8747
出典データセット
uspto-grants-1987_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04698337

反応ノート

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