Ethyl iodoacetate → [2-(2,5-Difluoro-phenyl)-ethoxy]-acetic acid ethyl ester

HRID 2100478Notes

Reaction equation

HRID 2100478 reaction equation
I[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[F:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[CH2:16][CH2:17][OH:18].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>ClCCl.FC(F)(F)S([O-])(=O)=O.[Ag+]>[CH2:6]([O:5][C:3](=[O:4])[CH2:2][O:18][CH2:17][CH2:16][C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[F:8])[CH3:7]

Participants

6

Reactant 3

HCID 12183Ethyl iodoacetateHCID 685102,6-Di-tert-butylpyridineHCID 179993612-(2,5-Difluorophenyl)ethanol

Product 1

HCID 67099228[2-(2,5-Difluoro-phenyl)-ethoxy]-acetic acid ethyl esterYield 54.2%

Reagents, catalysts & solvents 2

HCID 76223Silver(I) trifluoromethanesulfonateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Ethyl iodoacetate (340 μg, 12.9 mmol) was added to an ice cold solution of 2-(2,5-difluoro-phenyl)-ethanol (500 mg, 2.4 mmol), silver trifluoromethanesulfonate (685 mg, 2.7 mmol) and 2,6-di-tert-butylpyridin (820 μl, 3.6 mmol) in dichloromethane (5 ml). The reaction mixture was stirred at ambient temperature for 14 h, diluted with dichloromethane and filtered over speedex. Ice water/0.1 N aqueous HCl 1/1 was added to the filtrate and the filtrate was extracted two times with dichloromethane. The combined extracts were washed with aqueous NaHCO3 solution and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure left a colorless oil which was purified by column chromatography (silica gel, isopropyl acetate/heptane) to give [2-(2,5-difluoro-phenyl)-ethoxy]-acetic acid ethyl ester (320 mg, 1.3 mmol; 54%) as colorless oil. MS: m/e=245.0 [M+H+].

Workup

  1. filtrationfiltered over speedex
  2. additionIce water/0.1 N aqueous HCl 1/1 was added to the filtrate
  3. extractionthe filtrate was extracted two times with dichloromethane
  4. washThe combined extracts were washed with aqueous NaHCO3 solution and brine
  5. dry with materialdried over sodium sulfate
  6. customRemoval of the solvent under reduced pressure
  7. waitleft a colorless oil which
  8. customwas purified by column chromatography (silica gel, isopropyl acetate/heptane)

Sources & evidence

ORD record
ord-d94227ce98254084a9050ade4f879f56
Source dataset
uspto-grants-2009_08
Patent number
US07572801B2

Reaction notes

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