Cesium carbonate → 6-(3-Chlorophenyl)-5-(tetrahydrofuran-2-yl)-pyridine-2-carboxylic acid methyl ester

HRID 927543Notes

Reaction equation

HRID 927543 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:15][CH2:14][CH2:13][O:12]2)=[C:7](Br)[N:6]=1)=[O:4].[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(Cl)Cl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:15][CH2:14][CH2:13][O:12]2)=[C:7]([C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:17])[CH:23]=2)[N:6]=1)=[O:4]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 866747656-Bromo-5-(tetrahydrofuran-2-yl)-pyridine-2-carboxylic acid methyl ester

Product 1

HCID 710876046-(3-Chlorophenyl)-5-(tetrahydrofuran-2-yl)-pyridine-2-carboxylic acid methyl esterYield 94.4%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 6-bromo-5-(tetrahydrofuran-2-yl)-pyridine-2-carboxylic acid methyl ester (mixture of example 101d, 0.296 g, 1 mmol), 3-chlorophenylboronic acid (CAN 63503-60-6, 0.24 g, 1.5 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride methylene chloride complex (CAN 95464-05-4, 34 mg) and cesium carbonate (CAN 534-17-8, 1 g, 3 mmol) in DMF (10 mL) was stirred overnight at 80° C. under a nitrogen atmosphere. After filtration, the reaction mixture was poured into 20 mL H2O and washed with ethyl acetate (2×20 mL). The organic layer was concentrated under reduced pressure to provide the title compound (0.3 g, 91%) as black oil which was used in the next step without further purification; MS (EI): m/e=318.1 [M+H]+.

Workup

  1. filtrationAfter filtration
  2. additionthe reaction mixture was poured into 20 mL H2O
  3. washwashed with ethyl acetate (2×20 mL)
  4. concentrationThe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-931fe7659e654cb0857a0e710285c89b
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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