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

HRID 727616Notes

Reaction equation

HRID 727616 reaction equation
C1(P(Cl)(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(C(C)C)CC)(C)C.[OH:25][C@@H:26]([C@H:28]1[C:49](=[O:50])[N:30]2[CH:31]([C:36]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=3)=[O:37])[C:32](=O)[C@H:33]([CH3:34])[C@H:29]12)[CH3:27].[OH:51][CH2:52][CH2:53][N:54]1[CH2:59][CH2:58][N:57]([C:60]([C@@H:62]2[CH2:66][C@H:65]([SH:67])[CH2:64][N:63]2[C:68]([O:70][CH2:71][C:72]2[CH:77]=[CH:76][C:75]([N+:78]([O-:80])=[O:79])=[CH:74][CH:73]=2)=[O:69])=[O:61])[CH2:56][CH2:55]1>C(#N)C>[OH:51][CH2:52][CH2:53][N:54]1[CH2:55][CH2:56][N:57]([C:60]([C@@H:62]2[CH2:66][C@H:65]([S:67][C:32]3[C@H:33]([CH3:34])[C@@H:29]4[C@@H:28]([C@H:26]([OH:25])[CH3:27])[C:49](=[O:50])[N:30]4[C:31]=3[C:36]([O:38][CH2:39][C:40]3[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=3)=[O:37])[CH2:64][N:63]2[C:68]([O:70][CH2:71][C:72]2[CH:73]=[CH:74][C:75]([N+:78]([O-:80])=[O:79])=[CH:76][CH:77]=2)=[O:69])=[O:61])[CH2:58][CH2:59]1

Participants

6

Reactant 4

HCID 73910Diphenylphosphinic chlorideHCID 81531Diisopropylethylamine2×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 15282197(2S,4S)-2-[4-(2-Hydroxyethyl)-1-piperazinylcarbonyl]-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Product 1

HCID 152821984-Nitrobenzyl (1R,5S,6S)-2-[(2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateYield 52.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

1.82 ml of diphenylphosphoryl chloride and 1.54 ml of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 3.0 g of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 38 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. 1.54 ml of diisopropylethylamine and a solution of 3.63 g of (2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 54) in 30 ml of dry acetonitrile were then simultaneously added dropwise to the mixture, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 3 hours, after which it was allowed to stand overnight in a refrigerator. At the end of this time, the reaction mixture was worked up in a similar manner to that described in Example 49(b). The crude product was then purified by column chromatography through silica gel, using a 2:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 3.4 g of the title compound, as a powder. The infrared absorption spectrum and nuclear magnetic resonance spectrum of the product were identical with those of the compound prepared as described in step 54(i), above.

Workup

  1. temperaturecooling
  2. stirringthe resulting mixture was stirred at the same temperature for 3 hours
  3. waitto stand overnight in a refrigerator
  4. customThe crude product was then purified by column chromatography through silica gel
  5. additionby volume mixture of ethyl acetate and methanol as the eluent

Sources & evidence

ORD record
ord-fe0797f98fe84cafb5751cbe93d1035f
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

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