Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-cephem-4-carboxylate

HRID 615767ノート

反応式

HRID 615767 の反応式
P(Cl)(Cl)(Cl)=O.[O:6]1[C:11]([C:12](=[N:16][O:17][CH2:18][CH2:19][CH3:20])[C:13]([OH:15])=O)=[CH:10][S:9][CH2:8][CH2:7]1.[NH2:21][CH:22]1[C:42](=[O:43])[N:24]2[C:25]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:30])=[CH:26][CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[O:6]1[C:11]([C:12](=[N:16][O:17][CH2:18][CH2:19][CH3:20])[C:13]([NH:21][CH:22]2[C:42](=[O:43])[N:24]3[C:25]([C:29]([O:31][CH2:32][C:33]4[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=4)=[O:30])=[CH:26][CH2:27][S:28][C@H:23]23)=[O:15])=[CH:10][S:9][CH2:8][CH2:7]1

参加物

9

反応物 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylateHCID 537836602-(2,3-Dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid

生成物 1

HCID 1317120154-Nitrobenzyl 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-cephem-4-carboxylate収率 83.1%

試薬・触媒・溶媒 3

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

実験手順

Dry N,N-dimethylformamide (1.26 ml.), phosphoryl chloride (1.48 ml.), 2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid (syn isomer, 3.48 g.) and dry ethyl acetate (5 ml.) were treated in a conventional manner to give an activated acid solution. On the other hand, a solution of 4-nitrobenzyl 7-amino-3-cephem-4-carboxylate (5.0 g.) trimethylsilylacetamide (12.6 g.) and bis(trimethylsilyl)acetamide (8.3 g.) in ethyl acetate (700 ml.) was stirred at 40° C. for an hour. The activated acid solution was added all at once to the solution at -30° C. and stirred at -10° to -30° C. for 2 hours. After adding water (50 ml.) to the resultant solution, the ethyl acetate layer was separated. The solution was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diisopropyl ether, and the precipitates were collected by filtration and washed with diisopropyl ether to give 4-nitrobenzyl 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-cephem-4-carboxylate (syn isomer, 6.80 g.).

後処理

  1. customto give an activated acid solution
  2. additionThe activated acid solution was added all at once to the solution at -30° C.
  3. customthe ethyl acetate layer was separated
  4. washThe solution was washed with a saturated aqueous solution of sodium bicarbonate
  5. dry with materiala saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. filtrationthe precipitates were collected by filtration
  8. washwashed with diisopropyl ether

出典と根拠

ORDレコード
ord-c0b8d79500f24ab99308b75bde299097
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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