Ethyl Acetate → 4-Chloro-3-(2-(4-fluorophenyl)-3-(methoxycarbonyl)furo[2,3-b]pyridin-5-yl)benzoic acid

HRID 219398Notes

Reaction equation

HRID 219398 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:46]=[CH:47][C:48]=3[Cl:49])[C:43]([OH:45])=[O:44])[CH:38]=2)[O:33][C:32]=1[C:50]1[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=1.[C:57]([O:60][CH2:61]C)(=[O:59])C>CO.CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:49][C:48]1[CH:47]=[CH:46][C:42]([C:43]([OH:45])=[O:44])=[CH:41][C:40]=1[C:37]1[CH:38]=[C:39]2[C:31]([C:57]([O:60][CH3:61])=[O:59])=[C:32]([C:50]3[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=3)[O:33][C:34]2=[N:35][CH:36]=1

Participants

7

Reactant 3

HCID 8857Ethyl AcetateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 672176753-(3-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-chlorobenzoic acid

Product 1

HCID 672177944-Chloro-3-(2-(4-fluorophenyl)-3-(methoxycarbonyl)furo[2,3-b]pyridin-5-yl)benzoic acidYield 67%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

1,3-bis(diphenylphosphino)propane (28 mg, 0.067 mmol) was added to a stirring solution of palladium(II) acetate (7.5 mg, 0.034 mmol) and 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-chlorobenzoic acid (75 mg, 0.17 mmol) in MeOH (0.6 mL) and DMSO (1.1 mL) at 80° C. in a Parr bomb which was charged with 150 psi CO (g) and allowed to stir overnight. The mixture was diluted with ethyl acetate and washed with 1M HCl, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated to give the expected product 4-chloro-3-(2-(4-fluorophenyl)-3-(methoxycarbonyl)furo[2,3-b]pyridin-5-yl)benzoic acid (75 mg, 0.113 mmol, 67% yield) by LCMS. LC-MS retention time: 2.28 min; m/z (MH+): 427. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 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 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. additionwas charged with 150 psi CO (g)
  2. washwashed with 1M HCl
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-22816099a43b46fb970836656fa60971
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

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