2-Bromopyridine → [2,3'-Bipyridine]-6'-carboxylic acid

HRID 41295Notes

Reaction equation

HRID 41295 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:16]2[CH:17]=[CH:18][C:19]([C:22]([O:24]C)=[O:23])=[N:20][CH:21]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.C(O)C>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:16]1[CH:21]=[N:20][C:19]([C:22]([OH:24])=[O:23])=[CH:18][CH:17]=1

Participants

9

Reactant 4

HCID 79732-BromopyridineHCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 467386632-Methoxycarbonyl-5-pyridineboronic acid, pinacol ester

Product 1

HCID 57358853[2,3'-Bipyridine]-6'-carboxylic acidYield 23.2%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

In a 5 ml microwave vial were added 2-bromopyridine (0.093 ml, 0.949 mmol), methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinecarboxylate (300 mg, 1.139 mmol), bis(triphenylphosphine)palladium(II) chloride (133 mg, 0.190 mmol), sodium carbonate (302 mg, 2.85 mmol), 1,2-dimethoxyethane (1.5 ml), ethanol (1.000 ml) and water (0.500 ml). The reaction mixture was heated for 0.5 hours at 120° C. in the microwave. The mixture was diluted with MeOH and filtered through Celite®. The product was concentrated in vacuo then filtered through a 20 g SCX cartridge (washed with MeOH, eluted with 1M NH3 in MeOH) and evaporated in vacuo. The product was triturated with ether and concentrated under vacuo. The product was diluted in DCM then 1 ml of 1M HCl in ether added and the product was concentrated in vacuo then was dissolved in MeCN/DMSO 1:1 and purified by MDAP. The desired fractions were collected and concentrated under vacuo to give the title compound (44 mg).

Workup

  1. filtrationfiltered through Celite®
  2. concentrationThe product was concentrated in vacuo
  3. filtrationthen filtered through a 20 g SCX cartridge (washed with MeOH, eluted with 1M NH3 in MeOH)
  4. customevaporated in vacuo
  5. customThe product was triturated with ether
  6. concentrationconcentrated under vacuo
  7. additionThe product was diluted in DCM
  8. addition1 ml of 1M HCl in ether added
  9. concentrationthe product was concentrated in vacuo
  10. dissolutionthen was dissolved in MeCN/DMSO 1:1
  11. custompurified by MDAP
  12. customThe desired fractions were collected
  13. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-9ecab71c57fd40988bfeff16b7449608
Source dataset
uspto-grants-2013_09
Patent number
US08530478B2

Reaction notes

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