Dimethyl Sulfate → 2-Methoxy-6-methyl-benzoic acid ethyl ester

HRID 1582280Notes

Reaction equation

HRID 1582280 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([OH:13])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].O.[OH-].[Li+].S(OC)(O[CH3:21])(=O)=O>C1COCC1.C(OCC)C>[CH3:21][O:13][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([CH3:1])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 168937Lithium hydroxide, monohydrateHCID 584222Ethyl 2-hydroxy-6-methylbenzoate

Product 1

HCID 5910602-Methoxy-6-methyl-benzoic acid ethyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 6-methylsalicylate (1.27 g, 6.97 mmol) in THF (35 mL) was added lithium hydroxide monohydrate (0.594 g, 14.2 mmol) followed by dimethyl sulfate (1.00 mL, 10.6 mmol). The resultant mixture was heated to reflux for 1 hour then cooled to room temperature. The mixture was diluted with diethyl ether (70 mL), washed with saturated aqueous NaHCO3 (4×10 mL), dried (MgSO4) and concentrated. Purification of the crude material by column chromatography on silica gel (9:1 hexanes-EtOAc) provided 1.23 g (91%) of ethyl 2-methoxy-6-methylbenzoate as a white solid. 1H NMR (CDCl3) δ1.38 (t, 3H, J=7.2 Hz), 2.30 (s, 3H), 3.82 (s, 3H), 4.40 (q, 2H, J=7.2 Hz), 6.76 (d, 1H, J=8.4 Hz), 6.79 (d, 1H, J=7.8 Hz), 7.23 (dd, 1H, J=7.8, 8.4 Hz).

Workup

  1. temperatureto reflux for 1 hour
  2. washwashed with saturated aqueous NaHCO3 (4×10 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customPurification of the crude material by column chromatography on silica gel (9:1 hexanes-EtOAc)

Sources & evidence

ORD record
ord-26a7987071d54cbb872ce65ae9f9d654
Source dataset
uspto-grants-2004_05
Patent number
US06734191B2

Reaction notes

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