Cesium carbonate → 6-Phenylpyridine-2-carboxylic Acid

HRID 347535Notes

Reaction equation

HRID 347535 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][CH:3]=1.[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[C:11]1([C:2]2[N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][CH:3]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 5939196-Bromopyridine-2-carboxylic acid

Product 1

HCID 27628846-Phenylpyridine-2-carboxylic AcidYield 18%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-bromopicolinic acid (2.02 g, 10 mmol), phenyboronic acid (1.22 g, 10 mmol), cesium carbonate (5.00 g) and PdCl2 [(t-Bu)2P(OH)]2 (70 mg, CombiPhos Catalysts, Inc. Princeton, N.J.) in DMF (20 mL) and water (3 mL) was purged with Ar-gas and heated at 110° C. for 24 h. The reaction was incomplete and did not progress further. To the reaction mixture were added EtOAc (200 mL) and 1 N aq. HCl (40 mL). The EtOAc layer was separated, and the aqueous layer was washed with EtOAc (150 mL). The combined EtOAc layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by preparative HPLC to afford the desired product (350 mg, 18%) as a white solid. 1H NMR (CDCl3) δ 10.45 (s, 1H), 8.18–7.96 (m, 5H), 7.51–7.53 (m, 3H).

Workup

  1. customwas purged with Ar-gas
  2. additionTo the reaction mixture were added EtOAc (200 mL) and 1 N aq. HCl (40 mL)
  3. customThe EtOAc layer was separated
  4. washthe aqueous layer was washed with EtOAc (150 mL)
  5. dry with materialThe combined EtOAc layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-07df3be4d9a64c93af188128ddb6622b
Source dataset
uspto-grants-2007_02
Patent number
US07173031B2

Reaction notes

Loading…