Reaktion #671276

Reaktionsgleichung

Hydrazine acetate

(2S,4S)-4-acetylthio-2-[(3S)-3-[2-[2,3-bis(4-nitrobenzyloxycarbonyl)guanidino]acetylamino]pyrrolidin-1-ylcarbonyl]-1-methylpyrrolidine

4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-diphenylphosphoryloxy-1-carbapen-2-em-3-carboxylate

N,N-diisopropylethylamine

sodium hydrogencarbonate

→

desired compound

Ausbeute 66.1%

4-Nitrobenzyl (1R,5S,6S)-2-[(2S,4S)-2-[(3S)-3-[2-[2,3-bis(4-nitrobenzyloxy-carbonyl)guanidino]-acetylamino]pyrrolidin-1-ylcarbonyl]-1-methylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Ausbeute 66.1%

Lösungsmittel

tetrahydrofuran

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto react at −30° C. for 3 days
2. 2
   Filtrationthe resulting precipitate was filtered
3. 3
   Waschenwashed with water
4. 4
   workup.DISSOLUTIONdissolved in a mixture of tetrahydrofuran and ethyl acetate (3:7)
5. 5
   WaschenThe resulting solution was washed successively with saturated aqueous sodium hydrogencarbonate solution, water and saturated aqueous sodium chloride solution
6. 6
   Trocknendried over anhydrous magnesium sulfate
7. 7
   Einengenconcentrated in vacuo
8. 8
   SonstigeThe resulting residue was chromatographed on a silica gel column
9. 9
   Sonstigeto afford the crude desired product
10. 10
    Sonstigereprecipitated with a mixture of ethyl acetate and ether (1:1)

Vorschrift

Hydrazine acetate (652 mg) was added to a solution of (2S,4S)-4-acetylthio-2-[(3S)-3-[2-[2,3-bis(4-nitrobenzyloxycarbonyl)guanidino]acetylamino]pyrrolidin-1-ylcarbonyl]-1-methylpyrrolidine (4.3 g) in N,N-dimethylformamide (86 ml) and stirred at room temperature for 4 hours. To the resulting mixture was added 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-diphenylphosphoryloxy-1-carbapen-2-em-3-carboxylate (3.53 g) and N,N-diisopropylethylamine (1.34 ml) and allowed to react at −30° C. for 3 days. At the end of this time, to the reaction mixture was added 1% aqueous sodium hydrogencarbonate solution and the resulting precipitate was filtered, washed with water, and dissolved in a mixture of tetrahydrofuran and ethyl acetate (3:7). The resulting solution was washed successively with saturated aqueous sodium hydrogencarbonate solution, water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was chromatographed on a silica gel column using 10% methanol/ethyl acetate and 20% methanol/ethyl acetate as the eluant to afford the crude desired product. The product was dissolved in tetrahydrofuran and reprecipitated with a mixture of ethyl acetate and ether (1:1) to give the desired compound (4.02 g) as a pale yellow powder.

Quelle