Chloride → (5R, 6S)-2-[(2S, 4S)-1,1,-Dimethyl-2-(N,N-dimethylcarbamoyl)pyrrolidinium-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate

HRID 5061

反応式

HRID 5061 の反応式
[Cl-].[OH:2][C@@H:3]([C@H:5]1[C:25](=[O:26])[N:7]2[CH:8]([C:12]([O:14]CC3C=CC([N+]([O-])=O)=CC=3)=[O:13])[C:9](=O)[CH2:10][C@H:6]12)[CH3:4].[CH3:27][N:28]([CH3:39])[C:29]([C@@H:31]1[CH2:35][C@H:34]([SH:36])[CH2:33][N+:32]1([CH3:38])[CH3:37])=[O:30]>C(#N)C.C(N(C(C)C)CC)(C)C.O1CCCC1.P([O-])([O-])([O-])=O.[Pd]>[CH3:38][N+:32]1([CH3:37])[CH2:33][C@@H:34]([S:36][C:9]2[CH2:10][C@@H:6]3[C@@H:5]([C@H:3]([OH:2])[CH3:4])[C:25](=[O:26])[N:7]3[C:8]=2[C:12]([O-:14])=[O:13])[CH2:35][C@H:31]1[C:29](=[O:30])[N:28]([CH3:27])[CH3:39]

参加物

9

反応物 3

HCID 312ChlorideHCID 11198839(4-Nitrophenyl)methyl (5R,6S)-6-((1R)-1-hydroxyethyl)-3,7-dioxo-1-azabicyclo(3.2.0)heptane-2-carboxylateHCID 131717288(2S, 4S)-2-(N,N-dimethylcarbamoyl)-1,1-dimethyl-4-mercaptopyrrolidinium

生成物 1

HCID 131717287(5R, 6S)-2-[(2S, 4S)-1,1,-Dimethyl-2-(N,N-dimethylcarbamoyl)pyrrolidinium-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate収率 22.5%

試薬・触媒・溶媒 5

HCID 1061Phosphate溶媒HCID 6342Acetonitrile溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 23938Palladium溶媒HCID 81531Diisopropylethylamine溶媒2 回

実験手順

126 μl of diisopropylethylamine and 132 μl of diphenylphophoryl chloride were simultaneously added, whilst ice-cooling, to a solution of 218 mg of 4-nitrobenzyl (5R, 6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate dissolved in 3 ml of dry acetonitrile, and the mixture was stirred at the same temperature for 1 hour. At the end of this time, a solution of 243 mg of the crude (2S, 4S)-2-(N,N-dimethylcarbamoyl)-1,1-dimethyl-4-mercaptopyrrolidinium salt [prepared as described in Example 4-(1)] in 2 ml of dry acetonitrile and 144 μl of diisopropylethylamine were added to the mixture, whilst ice-cooling. The mixture was then allowed to stand at the same temperature for 5 hours and then for 2 days in a refrigerator. At the end of this time, the reaction mixture was worked up in a similar manner to that described in Example 6. The crude product was dissolved in a mixture of 15 ml of tetrahydrofuran and 15 ml of a 0.1M phosphate buffer (pH 7.0) and hydrogenated at room temperature for 2 hours in the presence of 200 mg of 10% w/w palladium-on-charcoal. At the end of this time, the reaction mixture was worked up and purified in a similar manner to that described in Example 6, to afford 56 mg of the title compound.

後処理

  1. temperaturecooling
  2. waitto stand at the same temperature for 5 hours
  3. waitfor 2 days in a refrigerator
  4. custompurified in a similar manner to that

出典と根拠

ORDレコード
ord-d999c5bb11f24db2a6563430a9eb42c7
出典データセット
uspto-grants-1993_09
特許番号
US05242914

関連ノート

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