Phosphorus oxychloride → 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 615761ノート

反応式

HRID 615761 の反応式
[O:1]1[C:6]([C:7](=[N:11][O:12][CH2:13][CH2:14][CH3:15])[C:8]([OH:10])=O)=[CH:5][S:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.[NH2:21][CH:22]1[C:40](=[O:41])[N:24]2[C:25]([C:37]([OH:39])=[O:38])=[C:26]([CH2:29][S:30][C:31]3[N:35]([CH3:36])[N:34]=[N:33][N:32]=3)[CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C>O.C(OCC)(=O)C.CN(C)C=O>[O:1]1[C:6]([C:7](=[N:11][O:12][CH2:13][CH2:14][CH3:15])[C:8]([NH:21][CH:22]2[C:40](=[O:41])[N:24]3[C:25]([C:37]([OH:39])=[O:38])=[C:26]([CH2:29][S:30][C:31]4[N:35]([CH3:36])[N:34]=[N:33][N:32]=4)[CH2:27][S:28][C@H:23]23)=[O:10])=[CH:5][S:4][CH2:3][CH2:2]1

参加物

8

反応物 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 537836602-(2,3-Dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid

生成物 1

HCID 1317120127-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid収率 83.4%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
40 °C

実験手順

2-(2,3-Dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid (syn isomer, 1.55 g.), dry N,N-dimethylformamide (0.56 ml.), dry ethyl acetate (2.1 ml.) and phosphoryl chloride (0.66 ml.) were treated in a conventional manner to give an activated acid solution. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (2 g.) and trimethylsilylacetamide (5.6 g.) were added to dry ethyl acetate (40 ml.) and stirred at 40° C. for an hour. To the solution was added the activated acid solution at -15° C. and stirred at -10° to -20° C. for 2 hours. Water (50 ml.) was added to the resultant solution and the ethyl acetate layer was separated. Water (30 ml.) was added to the ethyl acetate layer and adjusted to pH 7.5 with sodium bicarbonate. The aqueous layer was separated, washed with ethyl acetate and adjusted to pH 2.0 with 10% hydrochloric acid. The precipitates were collected by filtration, washed with water and dried over phosphorus pentoxide under reduced pressure to give 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2.75 g.).

後処理

  1. customto give an activated acid solution
  2. additionTo the solution was added the activated acid solution at -15° C.
  3. stirringstirred at -10° to -20° C. for 2 hours
  4. customthe ethyl acetate layer was separated
  5. additionWater (30 ml.) was added to the ethyl acetate layer and adjusted to pH 7.5 with sodium bicarbonate
  6. customThe aqueous layer was separated
  7. washwashed with ethyl acetate
  8. filtrationThe precipitates were collected by filtration
  9. washwashed with water
  10. dry with materialdried over phosphorus pentoxide under reduced pressure

出典と根拠

ORDレコード
ord-5f13475263974093b67689c56a5a82b6
出典データセット
uspto-grants-1985_02
特許番号
US04500709

反応ノート

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