Dimethyl Carbonate → 2-(Carboxymethyl)-4-methoxybenzoic acid

HRID 606307Notes

Reaction equation

HRID 606307 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([CH3:12])[CH:4]=1.[C:13](=O)([O:16]C)[O:14]C.[Li+].CC([N-]C(C)C)C>C1COCC1>[C:13]([CH2:12][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=[O:8])([OH:16])=[O:14]

Participants

5

Reactant 3

HCID 12021Dimethyl CarbonateHCID 5972164-Methoxy-2-methylbenzoic acidHCID 2724682Lithium diisopropylamide

Product 1

HCID 118166262-(Carboxymethyl)-4-methoxybenzoic acidYield 95.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-methoxy-2-methylbenzoic acid (10 g, 60 mmol) and dimethyl carbonate (10 ml, 120 mmol) in THF (80 ml) is added dropwise to LDA (120 ml of 2M in heptane/THF/ethylbenzene) at −78° C. The cold bath is removed, and after 4 h, water (100 ml) is added, and the resulting mixture is stirred overnight. After removal of organic solvents, the residue is acidified with c-HCl to pH 2. The resulting solid is filtered, dissolved in 1N—NaOH (80 ml), and then washed with ether (2×30 ml). The aqueous layer is acidified with c-HCl and the resulting white solid is filtered to give 12 g of 2-carboxymethyl-4-methoxy-benzoic acid. 1H NMR (DMSO) 12.3 (br s, 1H), 7.88 (d, 1H), 6.91 (d, 1H), 6.88 (s, 1H), 3.90 (s, 2H), 3.79 (s, 3H).

Workup

  1. customThe cold bath is removed
  2. additionwater (100 ml) is added
  3. customAfter removal of organic solvents
  4. filtrationThe resulting solid is filtered
  5. dissolutiondissolved in 1N—NaOH (80 ml)
  6. washwashed with ether (2×30 ml)
  7. filtrationthe resulting white solid is filtered

Sources & evidence

ORD record
ord-834643a1c95341a9b0ab4ab0ffd894db
Source dataset
uspto-grants-2011_03
Patent number
US07915288B2

Reaction notes

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