Isopropanol → 3-[(8-Amino-6-tetrazolo[1,5-b]pyridazinyl)-thiomethyl]-7-(4-chloro-3-oxobutyramido)-3-cephem-4-carboxylic acid

HRID 1065850

反応式

HRID 1065850 の反応式
[NH2:1][CH:2]1[C:24](=[O:25])[N:4]2[C:5]([C:21]([OH:23])=[O:22])=[C:6]([CH2:9][S:10][C:11]3[CH:12]=[C:13]([NH2:20])[C:14]4[N:15]([N:17]=[N:18][N:19]=4)[N:16]=3)[CH2:7][S:8][C@H:3]12.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[Cl:38][CH2:39][C:40](=[O:45])[CH2:41][C:42](Cl)=[O:43].C(O)(C)C>CN(C)C=O.C(Cl)Cl>[NH2:20][C:13]1[C:14]2[N:15]([N:17]=[N:18][N:19]=2)[N:16]=[C:11]([S:10][CH2:9][C:6]2[CH2:7][S:8][C@@H:3]3[CH:2]([NH:1][C:42](=[O:43])[CH2:41][C:40](=[O:45])[CH2:39][Cl:38])[C:24](=[O:25])[N:4]3[C:5]=2[C:21]([OH:23])=[O:22])[CH:12]=1

参加物

7

反応物 4

HCID 3776IsopropanolHCID 30162624-Chloro-3-oxobutyryl chlorideHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 1317127277-Amino-3-[(8-amino-6-tetrazolo[1,5-b]pyridazinyl)thiomethyl]-3-cephem-4-carboxylic acid

生成物 1

HCID 1317127263-[(8-Amino-6-tetrazolo[1,5-b]pyridazinyl)-thiomethyl]-7-(4-chloro-3-oxobutyramido)-3-cephem-4-carboxylic acid収率 92.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

7-Amino-3-[(8-amino-6-tetrazolo[1,5-b]pyridazinyl)thiomethyl]-3-cephem-4-carboxylic acid (3.8 g; 0.01 mole) was suspended in anhydrous N,N-dimethylformamide (50 ml) and N,O-bis(trimethylsilyl)acetamide (8.13 g; 0.04 mole) was added. After 2 hours of stirring at room temperature almost all the starting material was dissolved. A solution of 4-chloroacetoacetyl chloride (2.35 g; approximately 0.015 mole) in anhydrous methylene chloride (20 cc) was dropped into the cooled mixture (at -30° C.). The mixture was stirred at -30° C. for 2 hours and allowed to come to room temperature within an additional hour, after which time isopropanol (40 ml) was added, in order to decompose the silylated compounds. The solvents were evaporated under reduced pressure and the oily residue was partitioned between water and ethyl acetate. The organic layer was separated, washed with aqueous sodium chloride solution, concentrated to a small volume under reduced pressure, and diethyl ether was added to complete the precipitation. The solid was collected by filtration, washed with fresh ether and dried under vacuum, thus giving 4.6 g of the title compound, which was used in the following step without further purification.

後処理

  1. dissolutionwas dissolved
  2. stirringThe mixture was stirred at -30° C. for 2 hours
  3. waitto come to room temperature within an additional hour
  4. customThe solvents were evaporated under reduced pressure
  5. customthe oily residue was partitioned between water and ethyl acetate
  6. customThe organic layer was separated
  7. washwashed with aqueous sodium chloride solution
  8. concentrationconcentrated to a small volume under reduced pressure, and diethyl ether
  9. additionwas added
  10. customthe precipitation
  11. filtrationThe solid was collected by filtration
  12. washwashed with fresh ether
  13. customdried under vacuum

出典と根拠

ORDレコード
ord-a999cad4592840c4bba4ea16d2397ac4
出典データセット
uspto-grants-1982_05
特許番号
US04331666

関連ノート

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