Triphenylphosphine → HCID 131730268, compound

HRID 1967452Notes

Reaction equation

HRID 1967452 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][C:30]=1[O:31][CH3:32])[N:27]([C@H:33]([C:37]([CH3:45])([CH3:44])[O:38][SiH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH:34]([CH3:36])[CH3:35])[CH:26]=[C:25]([C:46]([O:48][CH2:49][CH3:50])=[O:47])[C:24]2=[O:51].[Br-].[Cl:53][C:54]1[C:55]([F:62])=[C:56]([CH:59]=[CH:60][CH:61]=1)[CH2:57][Zn+].[Cl-].[NH4+]>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1.CN1CCCC1=O>[C:40]([SiH2:39][O:38][C:37]([CH3:45])([CH3:44])[C@@H:33]([N:27]1[C:28]2[C:23](=[CH:22][C:21]([CH2:57][C:56]3[CH:59]=[CH:60][CH:61]=[C:54]([Cl:53])[C:55]=3[F:62])=[C:30]([O:31][CH3:32])[CH:29]=2)[C:24](=[O:51])[C:25]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:26]1)[CH:34]([CH3:35])[CH3:36])([CH3:43])([CH3:41])[CH3:42]

Participants

9

Reactant 4

HCID 11776TriphenylphosphineHCID 25517Ammonium ChlorideHCID 178469807HCID 178469807, compoundHCID 178505940HCID 178505940, compound

Product 1

HCID 131730268HCID 131730268, compound

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Under a nitrogen atmosphere, tris(dibenzylideneacetone)dipalladium(0) (332 mg) and triphenylphosphine (299 mg) were added to tetrahydrofuran (40 mL), and the mixture was stirred at room temperature for 1 hr. Ethyl 6-bromo-1-((S)-1-(tert-butyldimethyl-silanyloxymethyl)-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (10.0 g) obtained in Step 7 of Example 1/1-methyl-2-pyrrolidinone (80 mL) solution and a solution (26.2 g) of 29% 3-chloro-2-fluorobenzylzinc bromide in tetrahydrofuran were successively added dropwise at room temperature. After completion of the dropwise addition, the mixture was stirred at 65° C. for 3 hr, and the completion of the reaction was confirmed by HPLC. After cooling the reaction mixture, toluene (50 mL) and 12.5% aqueous ammonium chloride solution (100 mL) were added, sufficiently stirring, and the aqueous layer was discarded. The organic layer was washed successively with 25% aqueous ammonium chloride solution (50 mL), twice with 2% aqueous ethylenediamine solution (50 mL), and with 10% aqueous sodium chloride solution (50 mL). After washing, the solvent was evaporated under reduced pressure. Isopropanol (50 mL) was added to the concentrated residue to give a solution of ethyl 1-((S)-1-(tert-butyldimethyl-silanyloxymethyl)-2-methylpropyl)-6-(3-chloro-2-fluorobenzyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate in isopropanol. This was directly used in the next step.

Workup

  1. additionAfter completion of the dropwise addition
  2. stirringthe mixture was stirred at 65° C. for 3 hr
  3. additionwere added
  4. stirringsufficiently stirring
  5. washThe organic layer was washed successively with 25% aqueous ammonium chloride solution (50 mL), twice with 2% aqueous ethylenediamine solution (50 mL)
  6. washAfter washing
  7. customthe solvent was evaporated under reduced pressure
  8. additionIsopropanol (50 mL) was added to the concentrated residue

Sources & evidence

ORD record
ord-4cb02a5c264c46e0a27456fddf2746c0
Source dataset
uspto-grants-2013_04
Patent number
US08420821B2

Reaction notes

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