Phosphate → FR-27743

HRID 703605Notes

Reaction equation

HRID 703605 reaction equation
[F:1][CH2:2][CH2:3][O:4][CH2:5][C@@H:6]1[CH2:10][C@H:9]([S:11][C:12]2[C@H:18]([CH3:19])[C@H:17]3[N:14]([C:15](=[O:23])[C@@H:16]3[C@H:20]([OH:22])[CH3:21])[C:13]=2[C:24]([O:26]CC=C)=[O:25])[CH2:8][N:7]1C(OCC1C=CC([N+]([O-])=O)=CC=1)=O.C(C(CCCC)C([O-])=O)C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[H][H]>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[OH-].[Pd+2]>[F:1][CH2:2][CH2:3][O:4][CH2:5][C@@H:6]1[CH2:10][C@H:9]([S:11][C:12]2[C@H:18]([CH3:19])[C@H:17]3[N:14]([C:15](=[O:23])[C@@H:16]3[C@H:20]([OH:22])[CH3:21])[C:13]=2[C:24]([OH:26])=[O:25])[CH2:8][NH:7]1

Participants

9

Reactant 5

HCID 1061PhosphateHCID 11776TriphenylphosphineHCID 23672331Sodium 2-ethylhexanoateHCID 56978753allyl (4R,5S,6S)-3-[(2S,4S)-2-(2-fluoroethyloxymethyl)-1-(4-nitrobenzyloxycarbonyl)-pyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 86744488FR-27743Yield 53.2%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of allyl (4R,5S,6S)-3-[(2S,4S)-2-(2-fluoroethyloxymethyl)-1-(4-nitrobenzyloxycarbonyl)-pyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (4.00 g), sodium 2-ethylhexanoate (1.21 g), and triphenylphosphine (0.35 g) in tetrahydrofuran (120 ml) was added tetrakis(triphenylphosphine)palladium(0) (0.77 g) at ambient temperature in a stream of nitrogen. The mixture was stirred at the same condition for one hour. To the mixture was added 0.1M phosphate buffer (pH 6.0) (120 ml). The mixture was stirred in the presence of 20% palladium hydroxide on carbon (0.8 g) under atmospheric pressure of hydrogen at ambient temperature for 4 hours. The catalyst was filtered off and the filtrate was concentrated under reduced pressure to remove the tetrahydrofuran. An aqueous solution was washed with ethyl acetate (100 ml×3) and the organic solvent was removed by evaporation. The residual solution was subjected to a column chromatography on nonionic adsorption resin, "Diaion HP-20" (100 ml) and eluted with a mixture of acetone and water (7:93 V/V). The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-3-[(2S,4S)-2-(2-fluoroethyloxymethyl)pyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid as a solid (1.36 g). ##STR31##

Workup

  1. filtrationThe catalyst was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customto remove the tetrahydrofuran
  4. washAn aqueous solution was washed with ethyl acetate (100 ml×3)
  5. customthe organic solvent was removed by evaporation
  6. wash" (100 ml) and eluted with a mixture of acetone and water (7:93 V/V)
  7. additionThe fractions containing the desired compound
  8. customwere collected

Sources & evidence

ORD record
ord-ed1c668285bb405a8538a4983d35f5ef
Source dataset
uspto-grants-1991_01
Patent number
US04983596

Reaction notes

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