Hydrochloric Acid → [3-(4-Bromo-2-formyl-phenoxy)-phenyl]-acetic acid

HRID 885329Notes

Reaction equation

HRID 885329 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.[Br:12][C:13]1[CH:14]=[CH:15][C:16](F)=[C:17]([CH:20]=1)[CH:18]=[O:19].[H-].[Na+].Cl>CN(C=O)C>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([O:1][C:2]2[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=2)=[C:17]([CH:18]=[O:19])[CH:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 121223'-Hydroxyphenylacetic acidHCID 24758Sodium hydride2×HCID 7363275-Bromo-2-fluorobenzaldehyde2×

Product 1

HCID 58237510[3-(4-Bromo-2-formyl-phenoxy)-phenyl]-acetic acidYield 40.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

3-Hydroxyphenylacetic acid (3 g, 19.7 mmol) and 5-bromo-2-fluorobenzaldehyde (2.34 mL, 19.7 mmol) were combined in DMF (60 mL). Sodium hydride (60% in mineral oil; 1.58 g, 39.4 mmol) was added portionwise, and the reaction was stirred at 70° C. for 3 hours. Additional 5-bromo-2-fluorobenzaldehyde (2.34 mL, 19.7 mmol) and sodium hydride (60% in mineral oil; 0.79 g, 19.7 mmol) were added, and the reaction was stirred at 70° C. for 3 hours. The mixture was acidified with 1N aqueous HCl to pH 3-4 and extracted with EtOAc, and the combined organic layers were washed three times with H2O, dried and concentrated. The residue was purified by silica gel chromatography (20-40% EtOAc in hexanes) to give the desired product (2.7 g).

Workup

  1. stirringthe reaction was stirred at 70° C. for 3 hours
  2. extractionextracted with EtOAc
  3. washthe combined organic layers were washed three times with H2O
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (20-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-13b61ce5a9fe491081f78ebd95cee60b
Source dataset
uspto-grants-2012_08
Patent number
US08242145B2

Reaction notes

Loading…