Ethyl Acetate → 3-(2-(4-Fluorophenyl)-3-(methoxycarbonyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoic acid

HRID 219402

Reaktionsgleichung

Reaktionsgleichung von HRID 219402
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[CH3:49])[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[CH2:58][O:59][C:60](C)=[O:61]>CO.CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:56][C:53]1[CH:54]=[CH:55][C:50]([C:32]2[O:33][C:34]3=[N:35][CH:36]=[C:37]([C:40]4[CH:41]=[C:42]([CH:46]=[CH:47][C:48]=4[CH3:49])[C:43]([OH:45])=[O:44])[CH:38]=[C:39]3[C:31]=2[C:60]([O:59][CH3:58])=[O:61])=[CH:51][CH:52]=1

Komponenten

7

Edukt 3

HCID 8857Ethyl AcetateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 672171573-(3-Bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoic acid

Produkt 1

HCID 672175563-(2-(4-Fluorophenyl)-3-(methoxycarbonyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoic acidAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 887MethanolLösungsmittel

Versuchsvorschrift

1,3-bis(diphenylphosphino)propane (160 mg, 0.387 mmol) was added to a stirring solution of palladium(II) acetate (44 mg, 0.19 mmol) and 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoic acid (275 mg, 0.645 mmol) in MeOH (2.1 mL) and DMSO (4.3 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 EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and triturated with DCM to give the expected product 3-(2-(4-fluorophenyl)-3-(methoxycarbonyl)furo[2,3-b]pyridin-5-yl)-4-methylbenzoic acid (176 mg, 0.434 mmol, 67% yield) consistent by LCMS and NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.95 (1H, br. s.), 8.42 (1H, d, J=2.01 Hz), 8.34 (1H, d, J=2.01 Hz), 8.14-8.21 (2H, m), 7.93 (1H, dd, J=8.03, 1.76 Hz), 7.84 (1H, d, J=1.76 Hz), 7.45-7.53 (3H, m), 3.89 (3H, s), 2.32 (3H, s). LC-MS retention time: 2.16 min; m/z (MH+): 406. 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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-70a84eecf7af4d5d9686d55298082d99
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08198449B2

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