Acetic Acid → Razupenem

HRID 1374384Notes

Reaction equation

HRID 1374384 reaction equation
C(OC([N:7]1[C@@H:11]([CH3:12])[CH:10]=[C:9]([C:13]2[N:14]=[C:15]([S:18][C:19]3[C@H:25]([CH3:26])[C@H:24]4[N:21]([C:22](=[O:30])[C@@H:23]4[C@H:27]([OH:29])[CH3:28])[C:20]=3[C:31]([O:33]CC=C)=[O:32])[S:16][CH:17]=2)[CH2:8]1)=O)C=C.C(O)(=O)C.C([SnH](CCCC)CCCC)CCC.P([O-])([O-])([O-])=O>ClCCl>[OH:29][C@@H:27]([C@H:23]1[C:22](=[O:30])[N:21]2[C@@H:24]1[C@@H:25]([CH3:26])[C:19]([S:18][C:15]1[S:16][CH:17]=[C:13]([C:9]3[CH2:8][NH:7][C@@H:11]([CH3:12])[CH:10]=3)[N:14]=1)=[C:20]2[C:31]([OH:33])=[O:32])[CH3:28]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1061PhosphateHCID 5948TributylstannaneHCID 53375344HCID 53375344, compound

Product 1

HCID 10993211RazupenemYield 50.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of allyl (4R,5S,6S)-3-[(4-{(5S)-1-[(allyloxy)carbonyl]-5-methyl-2,5-dihydro-1H-pyrrol-3-yl}-1,3-thiazol-2-yl)sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (70 mg, 0.13 mmol) in dichloromethane (2 ml) were added acetic acid (19 μl) and tributyltin hydride (0.32 ml, 1.2 mmol) and added at room temperature bis(triphenylphosphine)palladium chloride(II) (91 mg, 0.013 mmol). Ten minutes later the reaction mixture was poured into a mixture of ice (10 g) and phosphate buffer (pH7.0, 10 ml). After separation of the mixture with a separating funnel, the organic layer was extracted twice with water and the aqueous layer was washed twice with dichloromethane (3 ml). The organic solvent in the aqueous layer was evaporated under reduced pressure, and the residue was purified by polymer chromatography (CHP-20P). The fractions eluted with 1–3% aqueous THF solution were combined and lyophilized to give (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-({4-[(5S)-5-methyl-2,5-dihydro-1H-pyrrol-3-yl}-1,3-thiazol-2-yl)sulfanyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (26.9 mg) as a white amorphous.

Workup

  1. customAfter separation of the mixture with a separating funnel
  2. extractionthe organic layer was extracted twice with water
  3. washthe aqueous layer was washed twice with dichloromethane (3 ml)
  4. customThe organic solvent in the aqueous layer was evaporated under reduced pressure
  5. customthe residue was purified by polymer chromatography (CHP-20P)
  6. washThe fractions eluted with 1–3% aqueous THF solution

Sources & evidence

ORD record
ord-fcd0132b7beb4be787899036335c614d
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

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