Dimethyl Sulfate → (5-Chloro-2-methoxyphenyl)acetic acid methyl ester

HRID 1450512Notes

Reaction equation

HRID 1450512 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH3:13])=[C:6]([CH2:8][C:9]([OH:11])=[O:10])[CH:7]=1.[C:14]([O-])([O-])=O.[K+].[K+].S(OC)(OC)(=O)=O>CC#N>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH3:13])=[C:6]([CH2:8][C:9]([O:11][CH3:14])=[O:10])[CH:7]=1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 15040472-(5-Chloro-2-methoxyphenyl)acetic acid

Product 1

HCID 10987645(5-Chloro-2-methoxyphenyl)acetic acid methyl esterYield 94.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A stirred suspension of (5-chloro-2-methoxyphenyl)acetic acid (10 g, 0.05 mol), anhydrous K2CO3 (8.3 g, 0.06 mol) and dimethyl sulfate (7.6 g, 0.06 mol) in anhydrous CH3CN (60 mL) was heated to reflux under nitrogen for 2 hours. The reaction mixture was allowed to cool and the excess dimethyl sulfate was quenched with Et3N (1 mL) and then filtered. The filtrate was rotary evaporated and the residue was suspended in water and extracted with ether, washed with satd. NaHCO3, water, brine and then dried (Na2SO4). Filtration and evaporation of the ether gave a colorless oil which was distilled in vacuo to afford methyl (5-chloro-2-methoxyphenyl)acetate (10.1 g, 94%): bp 96°-98° C./0.5 torr; IR (film, cm-1) 1742, 1250, 1150, 1028; 1H NMR (300 MHz, CDCl3)δ 3.56 (2 H, s), 3.66 (3 H, s), 3.76 (3 H, s), 8.75 (16 H, d, J=8.6 Hz), 7.13 (1 H, d, J=2.5 Hz), 7.17 (1 H, dd, J=8.6 and 2.5 Hz); MS m/e 215 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen for 2 hours
  3. temperatureto cool
  4. customthe excess dimethyl sulfate was quenched with Et3N (1 mL)
  5. filtrationfiltered
  6. customThe filtrate was rotary evaporated
  7. extractionextracted with ether
  8. washwashed with satd
  9. dry with materialNaHCO3, water, brine and then dried (Na2SO4)
  10. filtrationFiltration and evaporation of the ether
  11. customgave a colorless oil which
  12. distillationwas distilled in vacuo

Sources & evidence

ORD record
ord-693842b1d1de4ea0a17858297759bd3b
Source dataset
uspto-grants-1997_02
Patent number
US05602169

Reaction notes

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