1,3-Bis(diphenylphosphino)propane → HCID 67217142, compound

HRID 219411Notes

Reaction equation

HRID 219411 reaction equation
C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:31]1[C:39]2[C:34](=[N:35][CH:36]=[C:37]([C:40]3[CH:41]=[C:42]([CH:50]=[CH:51][C:52]=3[CH3:53])[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH:38]=2)[O:33][C:32]=1[C:54]1[CH:59]=[CH:58][C:57]([F:60])=[CH:56][CH:55]=1>CO.CS(C)=O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:46]([O:45][C:43]([C:42]1[CH:50]=[CH:51][C:52]([CH3:53])=[C:40]([C:37]2[CH:38]=[C:39]3[C:31]([C:43]([O:45][CH3:46])=[O:44])=[C:32]([C:54]4[CH:55]=[CH:56][C:57]([F:60])=[CH:58][CH:59]=4)[O:33][C:34]3=[N:35][CH:36]=2)[CH:41]=1)=[O:44])([CH3:48])([CH3:49])[CH3:47]

Participants

7

Reactant 2

HCID 812191,3-Bis(diphenylphosphino)propaneHCID 67217138Tert-butyl 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate

Product 1

HCID 67217142HCID 67217142, compoundYield 190.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,3-bis(diphenylphosphino)propane (119 mg, 0.287 mmol) was added to a stirring solution of palladium(II) acetate (32 mg, 0.144 mmol) and tert-butyl 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoate (231 mg, 0.479 mmol) in MeOH (1.6 mL) and DMSO (3 mL) at 80° C. in a PARR bomb which was then charged with 300 psi CO (g) and allowed to stir overnight. The mixture was diluted with EtOAc and filtered through a pad of celite. The filtrate was washed with sat. aq. NaHCO3, and brine. The organic phase was dried over Na2SO4, filtered and concentrated to give the expected product methyl 5-(5-(tert-butoxycarbonyl)-2-methylphenyl)-2-(4-fluorophenyl)furo[2,3-b]pyridine-3-carboxylate (211 mg, 0.457 mmol, 95% yield) crude by LCMS which was used directly in the next step. LC-MS retention time: 2.32 min; m/z (MH+): 462. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 mM, a hold time of 1 mM, and an analysis time of 4 min where solvent A was 5% MeOH/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. additionwas then charged with 300 psi CO (g)
  2. filtrationfiltered through a pad of celite
  3. washThe filtrate was washed with sat. aq. NaHCO3, and brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-b65333a5e3cc4a7c8895235f01802ab2
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

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