Phosphorus pentachloride → 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

HRID 1284654ノート

反応式

HRID 1284654 の反応式
P(Cl)(Cl)(Cl)(Cl)Cl.[C:7]([O:11][C:12]([CH2:14][O:15][N:16]=[C:17]([C:21]1[N:25]=[C:24]([NH2:26])[S:23][N:22]=1)[C:18]([OH:20])=O)=[O:13])([CH3:10])([CH3:9])[CH3:8].[NH2:27][CH:28]1[C:48](=[O:49])[N:30]2[C:31]([C:45]([OH:47])=[O:46])=[C:32]([CH2:35][S:36][C:37]3[N:41]([CH2:42][C:43]#[CH:44])[N:40]=[N:39][N:38]=3)[CH2:33][S:34][C@H:29]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:7]([O:11][C:12]([CH2:14][O:15][N:16]=[C:17]([C:21]1[N:25]=[C:24]([NH2:26])[S:23][N:22]=1)[C:18]([NH:27][CH:28]1[C:48](=[O:49])[N:30]2[C:31]([C:45]([OH:47])=[O:46])=[C:32]([CH2:35][S:36][C:37]3[N:41]([CH2:42][C:43]#[CH:44])[N:40]=[N:39][N:38]=3)[CH2:33][S:34][C@H:29]12)=[O:20])=[O:13])([CH3:8])([CH3:9])[CH3:10]

参加物

7

反応物 5

HCID 24819Phosphorus pentachlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 130511567-amino-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acidHCID 545194092-Tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid

生成物 1

HCID 1317130887-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid収率 59.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-10 °C

実験手順

To a solution of phosphorus pentachloride (2.50 g) in methylene chloride (60 ml) was added 2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid (syn isomer) (3.02 g) at -15° C. and the mixture was stirred for 45 minutes at -10° to -13° C. On the other hand, a mixture of 7-amino-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (3.52 g) and trimethylsilylacetamide (10 g) in methylene chloride (50 ml) was warmed to make a clear solution and then cooled to -10° C. The solution was added to the above activated mixture at a time and the mixture was stirred for 15 minutes at -5° to -10° C. The reaction mixture was poured into an aqueous solution (120 ml) of sodium bicarbonate (6.7 g) and stirred for 30 minutes at room temperature. The aqueous layer was separated and ethyl acetate was added thereto. The resulting mixture was adjusted to pH 3 with 6N hydrochloric acid. The ethyl acetate layer was separated, dried over magnesium sulfate and then evaporated. The residue was pulverized with isopropyl ether and then dried to give 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer)(3.8 g), mp. 120° to 125° C. (dec.).

後処理

  1. temperaturewas warmed
  2. additionThe solution was added to the above activated mixture at a time
  3. stirringthe mixture was stirred for 15 minutes at -5° to -10° C
  4. stirringstirred for 30 minutes at room temperature
  5. customThe aqueous layer was separated
  6. additionethyl acetate was added
  7. customThe ethyl acetate layer was separated
  8. dry with materialdried over magnesium sulfate
  9. customevaporated
  10. customdried

出典と根拠

ORDレコード
ord-49314c70c550479eb000f28a813af4d7
出典データセット
uspto-grants-1986_01
特許番号
US04563450

反応ノート

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