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 1492776Notes

Reaction equation

HRID 1492776 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-3ylmethyl)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-9aef0e8f9058480eb8c9b4855e5e0593
Source dataset
uspto-grants-1994_12
Patent number
US05374720

Reaction notes

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