Ethyl Acetate → allyl (1R,5S,6S)-2-[(2R, 4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

HRID 1755720Notes

Reaction equation

HRID 1755720 reaction equation
C(N(CC)C(C)C)(C)C.O(P(O[C:27]1[C@H:28]([CH3:44])[C@H:29]2[C@@H:39]([C@H:40]([OH:42])[CH3:41])[C:38](=[O:43])[N:30]2[C:31]=1[C:32]([O:34][CH2:35][CH:36]=[CH2:37])=[O:33])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[CH2:45]([O:48][C:49]([N:51]1[CH2:55][C@@H:54]([SH:56])[CH2:53][C@H:52]1[CH2:57][CH:58]1[CH2:62][CH2:61][NH:60][C:59]1=[O:63])=[O:50])[CH:46]=[CH2:47].C(OCC)(=O)C>C(#N)C>[CH2:45]([O:48][C:49]([N:51]1[CH2:55][C@@H:54]([S:56][C:27]2[C@H:28]([CH3:44])[C@@H:29]3[C@@H:39]([C@H:40]([OH:42])[CH3:41])[C:38](=[O:43])[N:30]3[C:31]=2[C:32]([O:34][CH2:35][CH:36]=[CH2:37])=[O:33])[CH2:53][C@H:52]1[CH2:57][CH:58]1[CH2:62][CH2:61][NH:60][C:59]1=[O:63])=[O:50])[CH:46]=[CH2:47]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 18657843(2R,4S)-N-allyloxycarbonyl-4-mercapto-2-(2-pyrrolidon-3ylmethyl)pyrrolidineHCID 57175810allyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Product 1

HCID 57051347allyl (1R,5S,6S)-2-[(2R, 4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateYield 51.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
5 °C

Procedure

N,N-diisopropylethylamine (0.26 ml, 1.52 mmol) was dropwise added to a solution of allyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (759 mg, 1.52 mmol) and (2R,4S)-N-allyloxycarbonyl-4-mercapto-2-(2-pyrrolidon-3-ylmethyl)pyrrolidine (432 mg, 1.52 mmol) in acetonitrile (11 ml) at -40° C. The reaction solution mixture was stirred at the same temperature for 3 hours and further at 5° C. for 16 hours. Ethyl acetate (60 ml) was added to the reaction solution. This solution mixture was washed sequentially with a saturated sodium hydrogen carbonate aqueous solution and a saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel flash column chromatography (Wakogel™ C-300, 40 ml, acetone-ethyl acetate 2:3), and the fraction containing the desired product was concentrated to obtain allyl (1R,5S,6S)-2-[(2R, 4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (420 mg, yield: 51.8%) in the form of foam.

Workup

  1. washThis solution mixture was washed sequentially with a saturated sodium hydrogen carbonate aqueous solution
  2. dry with materiala saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel flash column chromatography (Wakogel™ C-300, 40 ml, acetone-ethyl acetate 2:3)
  5. additionthe fraction containing the desired product
  6. concentrationwas concentrated

Sources & evidence

ORD record
ord-76b9f3ed2be3498a8320ae98e4df9f67
Source dataset
uspto-grants-1995_08
Patent number
US05438054

Reaction notes

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