Ethanol → (4R,5S,6S)-3-[(2S,4S)-2-(2-fluoropropyl)oxymethylpyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 703607Notes

Reaction equation

HRID 703607 reaction equation
C(OC([N:7]1[CH2:11][C@@H:10]([S:12][C:13]2[C@H:19]([CH3:20])[C@H:18]3[N:15]([C:16](=[O:24])[C@@H:17]3[C@H:21]([OH:23])[CH3:22])[C:14]=2[C:25]([O:27]CC=C)=[O:26])[CH2:9][C@H:8]1[CH2:31][O:32][CH2:33][CH:34]([F:36])[CH3:35])=O)C=C.C(O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1CCOCC1>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.O.C(OCC)(=O)C>[F:36][CH:34]([CH3:35])[CH2:33][O:32][CH2:31][C@@H:8]1[CH2:9][C@H:10]([S:12][C:13]2[C@H:19]([CH3:20])[C@H:18]3[N:15]([C:16](=[O:24])[C@@H:17]3[C@H:21]([OH:23])[CH3:22])[C:14]=2[C:25]([OH:27])=[O:26])[CH2:11][NH:7]1

Participants

9

Reactant 4

HCID 702EthanolHCID 8083MorpholineHCID 11776TriphenylphosphineHCID 86744491allyl (4R,5S,6S)-3-[(2S,4S)-1-allyloxycarbonyl-2-(2-fluoropropyl)oxymethylpyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

Product 1

HCID 18642561(4R,5S,6S)-3-[(2S,4S)-2-(2-fluoropropyl)oxymethylpyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acidYield 100.9%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of allyl (4R,5S,6S)-3-[(2S,4S)-1-allyloxycarbonyl-2-(2-fluoropropyl)oxymethylpyrrolidin-4-yl]thio-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (280 mg) in a mixture of tetrahydrofuran (2 ml), ethanol (1 ml) and water (200 μl) were added triphenylphosphine (14.2 mg), morpholine (125 μl) and tetrakis(triphenylphosphine)palladium(0) (12.2 mg) at room temperature for 3 hours under nitrogen atmosphere. The reaction mixture was poured into a mixture of ethyl acetate (20 ml) and water (10 ml). The aqueous layer was separated and concentrated in vacuo to give a residual solution, which was chromatographed on "Diaion HP-20" eluting in turn with water and 5% aqueous acetone. The fractions containing the desired compound were collected and lyophilized to give (4R,5S,6S)-3-[(2S,4S)-2-(2-fluoropropyl)oxymethylpyrrolidin-4-yl]thio-6-[( 1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (216 mg).

Workup

  1. customThe aqueous layer was separated
  2. concentrationconcentrated in vacuo
  3. customto give a residual solution, which
  4. customwas chromatographed on "Diaion
  5. wash" eluting in turn with water and 5% aqueous acetone
  6. additionThe fractions containing the desired compound
  7. customwere collected

Sources & evidence

ORD record
ord-3459313ded8d4ec8a00706df404dfb81
Source dataset
uspto-grants-1991_01
Patent number
US04983596

Reaction notes

Loading…