Potassium Phosphate, Tribasic → Methyl 2-(5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)acetate

HRID 40354

Reaction equation

HRID 40354 reaction equation
Cl[C:2]1[N:7]=[C:6]2[C:8]([CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:9][O:10][C:5]2=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[C:29]([F:31])[CH:30]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[F:24][C:25]1[CH:26]=[C:27]([C:2]2[N:7]=[C:6]3[C:8]([CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:9][O:10][C:5]3=[CH:4][CH:3]=2)[CH:28]=[C:29]([F:31])[CH:30]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 10198435Methyl 2-(5-chlorofuro[3,2-b]pyridin-3-yl)acetateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

Product 1

HCID 57691370Methyl 2-(5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)acetateYield 83.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
100 °C

Procedure

A sealable microwave vial was charged with methyl 2-(5-chlorofuro[3,2-b]pyridin-3-yl)acetate (1.30 g, 5.74 mmol), palladium(II) acetate (0.129 g, 0.574 mmol), potassium phosphate (3.66 g, 17.2 mmol), 3,5-difluorophenylboronic acid (1.81 g, 11.5 mmol), and X-Phos (0.548 g, 1.15 mmol). The vial was sealed, flushed with N2, then dioxane (20 mL) and H2O (2 mL) were added. The solution was sparged with N2 for 10 min, then heated at 100° C. for 24 h. The mixture was then cooled to rt and concentrated for purification by MPLC (Teledine Isco combiFlash Companion). The crude residue was taken up in minimal CH2Cl2 and absorbed onto a 25 g loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (120 g) using 98:2 Hexanes:EtOAc to 70:30 Hexanes:EtOAc gradient to afford methyl 2-(5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)acetate (1.46 g, 83.8% yield) as a colorless amorphous solid. LRMS (ESI) m/z calcd for C16H12F2NO3 (M+H) 304.1. found 304.2.

Workup

  1. customThe vial was sealed
  2. customflushed with N2
  3. additiondioxane (20 mL) and H2O (2 mL) were added
  4. customThe solution was sparged with N2 for 10 min
  5. temperatureThe mixture was then cooled to rt
  6. concentrationconcentrated for purification by MPLC (Teledine Isco combiFlash Companion)
  7. customabsorbed onto a 25 g loading cartridge

Sources & evidence

ORD record
ord-4842a4c343da4036b0a506afc74b64f2
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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