Methyl iodide → 4-[3-[6-(3-Bromo-5-methoxymethyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

HRID 416969Notes

Reaction equation

HRID 416969 reaction equation
[CH2:1]([O:3][C:4](=[O:38])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([CH2:28][OH:29])[CH:25]=[C:24]([Br:30])[CH:23]=2)[C:10]=1[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH3:2].[H-].[Na+].I[CH3:42]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:38])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([CH2:28][O:29][CH3:42])[CH:25]=[C:24]([Br:30])[CH:23]=2)[C:10]=1[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 594968024-[3-[6-(3-Bromo-5-hydroxymethyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

Product 1

HCID 594968044-[3-[6-(3-Bromo-5-methoxymethyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[3-[6-(3-bromo-5-hydroxymethyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (1.25 g, 2.1 mmol) in DMF (25 mL) were added sodium hydride (211 mg, 5.26 mmol) and iodomethane (747 mg, 5.26 mmol) at room temperature. The resulting suspension was stirred for 15 h and then the excess sodium hydride was quenched by slow addition of water (5 mL). The mixture was diluted with 1.0N hydrochloric acid (50 mL) and the organic compound was extracted into ethyl acetate (2×50 mL). The combined extracts were washed with brine solution (100 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under vacuum afforded the crude residue which was purified by using an ISCO 40 g column, eluting with 0-30% ethyl acetate in hexanes to obtain 4-[3-[6-(3-bromo-5-methoxymethyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (1.03 g, 81%) as a colorless viscous oil: EI(+)-HRMS m/e calcd for C31H43BrO7 (M+Na)+ 629.2084. found 629.2085.

Workup

  1. customthe excess sodium hydride was quenched by slow addition of water (5 mL)
  2. additionThe mixture was diluted with 1.0N hydrochloric acid (50 mL)
  3. extractionthe organic compound was extracted into ethyl acetate (2×50 mL)
  4. washThe combined extracts were washed with brine solution (100 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationFiltration of the drying agent and removal of the solvent under vacuum
  7. customafforded the crude residue which
  8. customwas purified
  9. washeluting with 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4683a0e39d7a45c48c5fe8fc08cf999d
Source dataset
uspto-grants-2012_01
Patent number
US08088936B2

Reaction notes

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