Diethyl Ether → Ethyl 2-ethoxy-4-iodobenzoate

HRID 2105848Notes

Reaction equation

HRID 2105848 reaction equation
C(=O)([O-])[O-].[K+].[K+].I[CH2:8][CH3:9].[OH:10][C:11]1[CH:19]=[C:18]([I:20])[CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=[O:14].[CH2:21](OCC)[CH3:22]>CC(=O)CC>[CH2:21]([O:10][C:11]1[CH:19]=[C:18]([I:20])[CH:17]=[CH:16][C:12]=1[C:13]([O:15][CH2:8][CH3:9])=[O:14])[CH3:22]

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 728742-Hydroxy-4-iodobenzoic acid

Product 1

HCID 29934691Ethyl 2-ethoxy-4-iodobenzoateYield 49%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (100 g, 724 mmol) and iodoethane (29.1 mL, 364 mmol) were added to a mechanically stirred solution of 2-hydroxy-4-iodobenzoic acid (16.0 g, 60.6 mmol, prepared according to Singh, S.; et al. J. Med. Chem. 1997, 40, 2472-2481) in 2-butanone (250 mL). The resulting mixture was heated at 80° C. for 16 h and then allowed to cool. Diethyl ether (250 mL) was added to the reaction vessel and the supernatant was transferred to a separatory funnel. Diethyl ether (250 mL) was again added to the reaction vessel to wash the remaining solid and the supernatant was again transferred to the separatory funnel. Water (400 mL) was added and the phases were separated. The aqueous phase was washed twice with diethyl ether (500 mL, 200 mL) and then the combined organic phases were washed with water (400 mL), brine (400 mL), dried over magnesium sulfate and concentrated. Purification of the crude residue by flash column chromatography (silica gel, eluting with 10% ethyl acetate in hexanes) gave ethyl 2-ethoxy-4-iodobenzoate as an off-white solid (9.50 g, 49%).

Workup

  1. temperatureto cool
  2. customthe supernatant was transferred to a separatory funnel
  3. washto wash the remaining solid
  4. additionWater (400 mL) was added
  5. customthe phases were separated
  6. washThe aqueous phase was washed twice with diethyl ether (500 mL, 200 mL)
  7. washthe combined organic phases were washed with water (400 mL), brine (400 mL)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. customPurification of the crude residue
  11. washby flash column chromatography (silica gel, eluting with 10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-0c1fe54e63ef42f7a024b83713f18a34
Source dataset
uspto-grants-2009_08
Patent number
US07579368B2

Reaction notes

Loading…