반응 #671276

ord-1ea670dc14044f8dbd0e357677c92c1a

반응 방정식

CC(=O)O.NN
Hydrazine acetate
CC(=O)S[C@H]1C[C@@H](C(=O)N2CC[C@H](NC(=O)CNC(=NC(=O)OCc3ccc([N+](=O)[O-])cc3)NC(=O)OCc3ccc([N+](=O)[O-])cc3)C2)N(C)C1
(2S,4S)-4-acetylthio-2-[(3S)-3-[2-[2,3-bis(4-nitrobenzyloxycarbonyl)guanidino]acetylamino]pyrrolidin-1-ylcarbonyl]-1-methylpyrrolidine
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(c3ccccc3)c3ccccc3)[C@H](C)[C@H]12
4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-diphenylphosphoryloxy-1-carbapen-2-em-3-carboxylate
CCN(C(C)C)C(C)C
N,N-diisopropylethylamine
O=C([O-])O.[Na+]
sodium hydrogencarbonate
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CC[C@H](NC(=O)CNC(=NC(=O)OCc5ccc([N+](=O)[O-])cc5)NC(=O)OCc5ccc([N+](=O)[O-])cc5)C4)N(C)C3)[C@H](C)[C@H]12
desired compound
수율 66.1%
C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CC[C@H](NC(=O)CNC(=NC(=O)OCc5ccc([N+](=O)[O-])cc5)NC(=O)OCc5ccc([N+](=O)[O-])cc5)C4)N(C)C3)[C@H](C)[C@H]12
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
수율 66.1%

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

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

실험 절차

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.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US06924279B2uspto-grants-2005_08