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

HRID 1755719Notes

Reaction equation

HRID 1755719 reaction equation
C(N(CC)C(C)C)(C)C.O(P(O[C:27]1[CH2:28][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.[CH2:44]([O:47][C:48]([N:50]1[CH2:54][C@@H:53]([SH:55])[CH2:52][C@H:51]1[CH2:56][CH:57]1[CH2:61][CH2:60][NH:59][C:58]1=[O:62])=[O:49])[CH:45]=[CH2:46].C(OCC)(=O)C>C(#N)C>[CH2:44]([O:47][C:48]([N:50]1[CH2:54][C@@H:53]([S:55][C:27]2[CH2:28][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])[CH2:52][C@H:51]1[CH2:56][CH:57]1[CH2:61][CH2:60][NH:59][C:58]1=[O:62])=[O:49])[CH:45]=[CH2:46]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 10624755allyl (5R,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylateHCID 18657843(2R,4S)-N-allyloxycarbonyl-4-mercapto-2-(2-pyrrolidon-3ylmethyl)pyrrolidine

Product 1

HCID 57230292allyl (5R,6S)-2-[(2R,4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylateYield 76.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N,N-diisopropylethylamine (0.13 ml, 0.76 mmol) was dropwise added to a solution of allyl (5R,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate (369 mg, 0.76 mmol) and (2R,4S)-N-allyloxycarbonyl-4-mercapto-2-(2-pyrrolidon-3-ylmethyl)pyrrolidine (216 mg, 0.76 mmol) in acetonitrile (5.6 ml) under cooling with ice. The reaction mixture solution was stirred at the same temperature for one hour and further stirred at 5° C. for 16 hours. Ethyl acetate (60 ml) was added to the reaction solution. The 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). The fraction containing the desired product was concentrated to obtain allyl (5R,6S)-2-[(2R,4S)-N-allyloxycarbonyl-2-(2-pyrrolidon-3-ylmethyl)pyrrolidin-4-ylthio]-6-[(R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate (303 mg, yield: 76.7%) in the form of foam.

Workup

  1. temperatureunder cooling with ice
  2. stirringfurther stirred at 5° C. for 16 hours
  3. washThe mixture was washed sequentially with a saturated sodium hydrogen carbonate aqueous solution
  4. dry with materiala saturated sodium chloride aqueous solution, then dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash column chromatography (Wakogel™ C-300, 40 ml, acetone-ethyl acetate 2:3)
  7. additionThe fraction containing the desired product
  8. concentrationwas concentrated

Sources & evidence

ORD record
ord-cfaf5cf9e6d04ecf9ef3c639eba79c33
Source dataset
uspto-grants-1995_08
Patent number
US05438054

Reaction notes

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