Diphenyl chlorophosphate → Allyl (5R,6S)-2-[(2S,4S)-N-allyloxycarbonyl-2-hydroxymethylpyrrolidin-4-ylthio]-6-[(R)-1-allyloxycarbonyloxyethyl]-1-carbapen-2-em-3-carboxylate

HRID 2371831Notes

Reaction equation

HRID 2371831 reaction equation
[CH2:1]([O:4][C:5]([O:7][C@@H:8]([C@H:10]1[C:23](=[O:24])[N:12]2[C@@H:13]([C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])[C:14](=O)[CH2:15][C@H:11]12)[CH3:9])=[O:6])[CH:2]=[CH2:3].C(N(CC)C(C)C)(C)C.P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[CH2:51]([O:54][C:55]([N:57]1[CH2:61][C@@H:60]([SH:62])[CH2:59][C@H:58]1[CH2:63][OH:64])=[O:56])[CH:52]=[CH2:53]>C(#N)C>[CH2:51]([O:54][C:55]([N:57]1[CH2:61][C@@H:60]([S:62][C:14]2[CH2:15][C@@H:11]3[C@@H:10]([C@H:8]([O:7][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[CH3:9])[C:23](=[O:24])[N:12]3[C:13]=2[C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18])[CH2:59][C@H:58]1[CH2:63][OH:64])=[O:56])[CH:52]=[CH2:53]

Participants

6

Reactant 4

HCID 75654Diphenyl chlorophosphateHCID 81531Diisopropylethylamine2×HCID 22842694(2S,4S)-N-Allyloxycarbonyl-2-hydroxymethyl-4-mercaptopyrrolidineHCID 131717188allyl (3R,5R,6S)-6-[(R)-1-allyloxycarbonyloxyethyl]-2-oxo-1-carbapenam-3-carboxylate

Product 1

HCID 57034286Allyl (5R,6S)-2-[(2S,4S)-N-allyloxycarbonyl-2-hydroxymethylpyrrolidin-4-ylthio]-6-[(R)-1-allyloxycarbonyloxyethyl]-1-carbapen-2-em-3-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of allyl (3R,5R,6S)-6-[(R)-1-allyloxycarbonyloxyethyl]-2-oxo-1-carbapenam-3-carboxylate (1.01 g, 3 mmol) and N,N-diisopropylethylamine (0.73 ml, 4.2 mmol) in acetonitrile (20 ml) was dropwise added diphenyl chlorophosphate (0.75-3.6 mmol) under ice-cooling, and then the mixture stirred for 30 minutes. The reaction mixture under ice-cooling was treated successively with N,N-diisopropylethylamine (0.73 μl, 4.2 mmol) and (2S,4S)-N-allyloxycarbonyl-2-hydroxymethyl-4-mercaptopyrrolidine (780 mg, 3.6 mmol) in acetonitrile (4 ml), stirred for 1 hour, and partitioned between ethyl acetate (60 ml) and water (40 ml). The organic layer was successively washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, concentrated, and the residue purified by flash column chromatography on silica gel (Wakogel® C-300, 40 ml, elution with ethyl acetate-hexane 1:1) to afford the title compound (1.20 g, 75% yield).

Workup

  1. temperaturecooling
  2. temperatureThe reaction mixture under ice-cooling
  3. stirringstirred for 1 hour
  4. custompartitioned between ethyl acetate (60 ml) and water (40 ml)
  5. washThe organic layer was successively washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customthe residue purified by flash column chromatography on silica gel (Wakogel® C-300, 40 ml, elution with ethyl acetate-hexane 1:1)

Sources & evidence

ORD record
ord-e8a6b138dfa144ac96d29c0780546b54
Source dataset
uspto-grants-1992_03
Patent number
US05095013

Reaction notes

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