Diisopropylethylamine → allyl (1R,5S,6S)-2-[(2S,4S)-N-allyloxycarbonyl-2-[(E)-2-(aminocarbonyl)vinyl]pyrrolidin-4-ylthio]-6-[(R)-1hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

HRID 2371817Notes

Reaction equation

HRID 2371817 reaction equation
O(P(O[C:18]1[C@H:19]([CH3:35])[C@H:20]2[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:21]2[C:22]=1[C:23]([O:25][CH2:26][CH:27]=[CH2:28])=[O:24])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[CH2:36]([O:39][C:40]([N:42]1[CH2:46][C@@H:45]([SH:47])[CH2:44][C@H:43]1/[CH:48]=[CH:49]/[C:50]([NH2:52])=[O:51])=[O:41])[CH:37]=[CH2:38].C(N(CC)C(C)C)(C)C>C(#N)C>[CH2:36]([O:39][C:40]([N:42]1[CH2:46][C@@H:45]([S:47][C:18]2[C@H:19]([CH3:35])[C@@H:20]3[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:21]3[C:22]=2[C:23]([O:25][CH2:26][CH:27]=[CH2:28])=[O:24])[CH2:44][C@H:43]1/[CH:48]=[CH:49]/[C:50]([NH2:52])=[O:51])=[O:41])[CH:37]=[CH2:38]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 57175810allyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateHCID 86745543(E)-3-[(2S,4S)-N-Allyloxycarbonyl-4-mercaptopyrrolidin-2-yl]acrylamide

Product 1

HCID 131717187allyl (1R,5S,6S)-2-[(2S,4S)-N-allyloxycarbonyl-2-[(E)-2-(aminocarbonyl)vinyl]pyrrolidin-4-ylthio]-6-[(R)-1hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylateYield 82.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of allyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (27.0 g, 54.06 mmol) and (E)-3-[(2S,4S)-N-allyloxycarbonyl-4-mercaptopyrrolidin-2-yl]acrylamide (16.63 g, 64.88 mmol) in acetonitrile (405 ml) was dropwise added N,N-diisopropylethylamine (9.42 ml, 54.06 mmol) at -30° C. over 15 minutes. The reaction mixture was stirred at -30° C. for 4 hours and at 5° C. for another 16 hours, partitioned between ethyl acetate (400 ml) and water (400 ml), and the each layer separated. The aqueous layer was treated with ethyl acetate (200 ml) for back extraction, the combined organic layer washed successively with saturated aqueous sodium bicarbonate (300 ml) and saturated aqueous sodium chloride (300 ml), dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel (Wakogel® C-300, 400 ml; elution with ethyl acetate-acetone 7:3) to afford allyl (1R,5S,6S)-2-[(2S,4S)-N-allyloxycarbonyl-2-[(E)-2-(aminocarbonyl)vinyl]pyrrolidin-4-ylthio]-6-[(R)-1hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate (22.64 g, 82.8% yield) as a foam powder.

Workup

  1. customat -30° C.
  2. customover 15 minutes
  3. custompartitioned between ethyl acetate (400 ml) and water (400 ml)
  4. customthe each layer separated
  5. additionThe aqueous layer was treated with ethyl acetate (200 ml) for back extraction
  6. washthe combined organic layer washed successively with saturated aqueous sodium bicarbonate (300 ml) and saturated aqueous sodium chloride (300 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography on silica gel (Wakogel® C-300, 400 ml; elution with ethyl acetate-acetone 7:3)

Sources & evidence

ORD record
ord-c10a53e074594f3aab85f2a62ed4acd7
Source dataset
uspto-grants-1992_03
Patent number
US05095013

Reaction notes

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