Dimethyl Sulfate → (E)-methyl 2-[2-(3-hydroxyphenoxy)phenyl]-3-methoxypropenoate

HRID 129590

Reaction equation

HRID 129590 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([O:17][CH3:18])=[O:16].[CH3:22][O:23][CH:24]=O.S(OC)(OC)(=O)=O>CN(C=O)C.O>[OH:3][C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1/[C:14](=[CH:22]\[O:23][CH3:24])/[C:15]([O:17][CH3:18])=[O:16]

Participants

7

Reactant 4

HCID 6497Dimethyl SulfateHCID 7865Methyl formateHCID 24758Sodium hydrideHCID 14620155Methyl 2-(3-hydroxyphenoxy)phenylacetate

Product 1

HCID 14620157(E)-methyl 2-[2-(3-hydroxyphenoxy)phenyl]-3-methoxypropenoate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (0.558 g, 0.023 moles in DMF (20 ml) was added dropwise a solution of methyl 2-(3-hydroxyphenoxy)phenylacetate (D) (2.0 g; 0.0077 mol) in DMF (10 ml) and methylformate (10 g; 0.167 mol) After stirring for 45 minutes, water (100 mls) was added and the mixture was extracted with ether (50 mls). The aqueous layer was acidified with hydrochloric acid to pH 3-4 and the mixture was extracted with ether (2×40 mls). The combined ether extracts were washed with water (3×30 mls) and saturated brine (1×30 ml), and then dried. The ether was evaporated off and the residue was dissolved in DMF (20 ml), and anhydrous potassium carbonate. (0.64 g; 0.0046 moles) and dimethyl sulphate (0.55 g; 0.0044 moles) was added. The mixture was stirred at ambient temperature for 1 hour, then water (100 ml) was added, and the mixture was extracted with ether (2×40 ml). The combined ether extracts were washed with water (3×20 ml) and saturated brine (20 ml), dried, filtered, evaporate to dryness, then chromatographed using a mixture of ether and hexane as eluant to give (E)-methyl 2-[2-(3-hydroxyphenoxy)phenyl]-3-methoxypropenoate (E) as an amber gum which, on trituration with a mixture of hexane and dichloromethane, gave a white solid, [0.7 g, 30% yield from methyl 2-(3-hydroxyphenoxy)phenylacetate (D)] m.p. 115°-116° C.

Workup

  1. extractionthe mixture was extracted with ether (50 mls)
  2. extractionthe mixture was extracted with ether (2×40 mls)
  3. washThe combined ether extracts were washed with water (3×30 mls) and saturated brine (1×30 ml)
  4. customdried
  5. customThe ether was evaporated off
  6. dissolutionthe residue was dissolved in DMF (20 ml)
  7. stirringThe mixture was stirred at ambient temperature for 1 hour
  8. extractionthe mixture was extracted with ether (2×40 ml)
  9. washThe combined ether extracts were washed with water (3×20 ml) and saturated brine (20 ml)
  10. customdried
  11. filtrationfiltered
  12. customevaporate to dryness
  13. customchromatographed
  14. additiona mixture of ether and hexane as eluant

Sources & evidence

ORD record
ord-8713442825dc47c6a39e01c746bb35eb
Source dataset
uspto-grants-1995_11
Patent number
US05468857

Linked notes

Loading…