2,5-Dihydrofuran → HCID 71087871, compound

HRID 632121Notes

Reaction equation

HRID 632121 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][N:6]=1)=[O:4].[O:12]1[CH2:16][CH:15]=[CH:14][CH2:13]1.C([O-])(=O)C.[Na+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>CN(C=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:14]2[CH2:13][O:12][CH2:16][CH:15]=2)=[CH:7][N:6]=1)=[O:4].[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:13]2[O:12][CH2:16][CH2:15][CH:14]=2)=[CH:7][N:6]=1)=[O:4]

Participants

8

Reactant 4

HCID 155702,5-DihydrofuranHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 517045Sodium AcetateHCID 7016458Methyl 5-bromopyridine-2-carboxylate

Product 2

HCID 71087871HCID 71087871, compoundYield 152.5%HCID 71087971HCID 71087971, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-bromo-pyridine-2-carboxylic acid methyl ester (CAN 29682-15-3, 15 g, 69 mmol), 2,5-dihydrofuran (CAN 36620-92-5, 48 g, 0.69 mol), palladium diacetate (CAN 3375-31-3, 0.8 g, 3.6 mmol), sodium acetate (6.9 g, 84 mmol) and tri-tert-butylphosphine (CAN 13716-12-6, 10%, 14 g, 7 mmol) in DMF (50 ml) was stirred at 120° C. in a sealed tube for 2.5 h. After cooling to room temperature, the reaction mixture was concentrated. The crude product was purified by column chromatography (silica gel, 200 g, eluting with 30% ethyl acetate in petroleum ether) to give 5-(2,5-dihydrofuran-3-yl)-pyridine-2-carboxylic acid methyl ester (a1) and 5-(4,5-dihydrofuran-2-yl)-pyridine-2-carboxylic acid methyl ester (a2) (mixture, a1/a2=1/0.94 at UV 254 nm, 10.8 g, 76%) as colorless oil; MS (EI): m/e=206.1 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated
  3. customThe crude product was purified by column chromatography (silica gel, 200 g, eluting with 30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-99b6c96f35e746329df0b19f8f177e0e
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Reaction notes

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