Diphenylphosphinic chloride → (1R,5S,6S)-2-[(2S,4S)-2-(1,1-Dimethyl-2-pyrrolidinioethylcarbamoyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate fluorosulfonate

HRID 37335

反応式

HRID 37335 の反応式
[OH:1][C@@H:2]([C@H:4]1[C:25](=[O:26])[N:6]2[CH:7]([C:12]([O:14]CC3C=CC([N+]([O-])=O)=CC=3)=[O:13])[C:8](=O)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].[C:27]1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.FC(F)(F)[S:53]([OH:56])(=[O:55])=[O:54].[F:59]C(F)(F)S(O)(=O)=O.[SH:67][C@@H:68]1[CH2:72][N:71](C(OCC2C=CC([N+]([O-])=O)=CC=2)=O)[C@H:70]([C:86](=[O:96])[NH:87][CH:88]([CH3:95])[CH2:89][N:90]2[CH2:94][CH2:93][CH2:92][CH2:91]2)[CH2:69]1>C(#N)C>[F:59][S:53]([O-:56])(=[O:55])=[O:54].[CH3:27][C:88]([NH:87][C:86]([C@@H:70]1[CH2:69][C@H:68]([S:67][C:8]2[C@H:9]([CH3:10])[C@@H:5]3[C@@H:4]([C@H:2]([OH:1])[CH3:3])[C:25](=[O:26])[N:6]3[C:7]=2[C:12]([OH:14])=[O:13])[CH2:72][NH:71]1)=[O:96])([CH3:95])[CH2:89][NH+:90]1[CH2:91][CH2:92][CH2:93][CH2:94]1

参加物

6

反応物 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2 回HCID 98853021-Azabicyclo[3.2.0]heptane-2-carboxylic acid, 6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-, (4-nitrophenyl)methyl ester, (4R,5R,6S)-HCID 86747836(2S, 4S)-4-Mercapto-2-(1-methyl-2-pyrrolidinylethylcarbamoyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine bis(trifluoromethanesulfonate)

生成物 1

HCID 131719012(1R,5S,6S)-2-[(2S,4S)-2-(1,1-Dimethyl-2-pyrrolidinioethylcarbamoyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate fluorosulfonate

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒2 回

実験手順

180 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate were dissolved in 2.3 ml of anhydrous acetonitrile, and the solution was placed on an ice bath. Maintaining the solution on the ice bath, 109 μl of diphenylphosphoryl chloride and 92 μl of diisopropylethylamine were added dropwise to the solution. The resulting mixture was then stirred for 1 hour at this ice-cooled temperature, after which, whilst still maintaining the reaction mixture on the ice bath, 313 μl of diisopropylethylamine and 1.9 ml of an anhydrous acetonitrile solution containing 440 mg of (2S,4S)-4-mercapto-2-(1-methyl-2-pyrrolidinylethylcarbamoyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine bis(trifluoromethanesulfonate) [prepared as described in step (1) above] were added dropwise to the mixture. The mixture was then stirred at this ice-cooled temperature for 5 hours and allowed to stand for 2 days in a refrigerator. At the end of this time, the solvent was removed by distillation under reduced pressure. An aqueous solution of sodium hydrogencarbonate was added to the residue, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was subjected to Lobar column chromatography (Merck, LiChroprep Si60). From fractions eluted with a 1:2 by volume mixture of acetonitrile and methanol were obtained 65 mg of the title compound.

後処理

  1. customthe solution was placed on an ice bath
  2. additionwere added dropwise to the solution
  3. temperaturecooled temperature
  4. additionwere added dropwise to the mixture
  5. temperaturecooled temperature for 5 hours
  6. customAt the end of this time, the solvent was removed by distillation under reduced pressure
  7. additionAn aqueous solution of sodium hydrogencarbonate was added to the residue, which
  8. extractionwas then extracted with ethyl acetate
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. customThe solvent was removed by distillation under reduced pressure
  11. washFrom fractions eluted with a 1:2 by volume mixture of acetonitrile

出典と根拠

ORDレコード
ord-e2c684d4cee5478788bcc5a161b9ba84
出典データセット
uspto-grants-1995_05
特許番号
US05420119

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