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

HRID 727716Notes

Reaction equation

HRID 727716 reaction equation
[CH3:1][N:2]([CH3:28])[CH:3]1[CH2:6][N:5]([C:7]([C@@H:9]2[CH2:13][C@H:12]([SH:14])[CH2:11][N:10]2[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=2)=[O:16])=[O:8])[CH2:4]1.C(N(C(C)C)CC)(C)C.C1(P(O[C:53]2[C@H:54]([CH3:77])[C@@H:55]3[C@@H:72]([C@H:73]([OH:75])[CH3:74])[C:71](=[O:76])[N:56]3[C:57]=2[C:58]([O:60][CH2:61][C:62]2[CH:67]=[CH:66][C:65]([N+:68]([O-:70])=[O:69])=[CH:64][CH:63]=2)=[O:59])(C2C=CC=CC=2)=O)C=CC=CC=1>C(#N)C>[CH3:1][N:2]([CH3:28])[CH:3]1[CH2:4][N:5]([C:7]([C@@H:9]2[CH2:13][C@H:12]([S:14][C:53]3[C@H:54]([CH3:77])[C@@H:55]4[C@@H:72]([C@H:73]([OH:75])[CH3:74])[C:71](=[O:76])[N:56]4[C:57]=3[C:58]([O:60][CH2:61][C:62]3[CH:63]=[CH:64][C:65]([N+:68]([O-:70])=[O:69])=[CH:66][CH:67]=3)=[O:59])[CH2:11][N:10]2[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=2)=[O:16])=[O:8])[CH2:6]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 15871605p-nitrobenzyl (1R,5R,6S)-2-(di-phenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylateHCID 57145492(2S,4S)-2-(3-Dimethylaminoazetidin-1-ylcarbonyl)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine

Product 1

HCID 1317204474-Nitrobenzyl (1R,5S,6S)-2-[(2S,4S)-2-(3-dimethylaminoazetidin-1-ylcarbonyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateYield 64.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of 0.98 g of (2S,4S)-2-(3-dimethylaminoazetidin-1-ylcarbonyl)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 121) dissolved in 20 ml of dry acetonitrile and 0.418 ml of diisopropylethylamine were added dropwise at the same time, whilst ice-cooling, to a solution of 1.43 g of 4-nitrobenzyl (1R,5R,6S)-2-(diphenylphosphoryloxy)-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (prepared as described in Preparation 123) in 25 ml of dry acetonitrile. The mixture was then stirred at the same temperature for 2 hours, after which it was left to stand in a refrigerator overnight. The reaction mixture was then concentrated by evaporation under reduced pressure, and the resulting residue was diluted with ethyl acetate; the resulting mixture was washed with water and then with an aqueous solution of sodium chloride. The ethyl acetate layer was dried over anhydrous magnesium sulfate and then concentrated by evaporation under reduced pressure. The residue was purified by silica gel column chromatography and the fractions obtained by elution with a 75:25 by volume mixture of ethyl acetate and methanol were combined and concentrated by evaporation under reduced pressure, to obtain 1.16 g of the title compound, as a powder.

Workup

  1. waitafter which it was left
  2. customto stand in a refrigerator overnight
  3. concentrationThe reaction mixture was then concentrated by evaporation under reduced pressure
  4. additionthe resulting residue was diluted with ethyl acetate
  5. washthe resulting mixture was washed with water
  6. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customThe residue was purified by silica gel column chromatography
  9. customthe fractions obtained by elution with a 75:25 by volume mixture of ethyl acetate and methanol
  10. concentrationconcentrated by evaporation under reduced pressure

Sources & evidence

ORD record
ord-7efee5fec37d421f8c4fba364faf4b07
Source dataset
uspto-grants-1998_01
Patent number
US05712267

Reaction notes

Loading…