Methyl iodide → 3-Methoxybenzoic Acid

HRID 330210Notes

Reaction equation

HRID 330210 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.CN(C)C(CCCC1C=C2C(=CC=1)N(CCC)C=C2C[C:33]1[CH:41]=[CH:40][C:36]([C:37]([OH:39])=[O:38])=[CH:35][C:34]=1[O:42][CH3:43])=O.CI>O1CCCC1>[CH3:43][O:42][C:34]1[CH:35]=[C:36]([CH:40]=[CH:41][CH:33]=1)[C:37]([OH:39])=[O:38]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 14882585HCID 14882585, compoundHCID 178418339Butyllithium

Product 1

HCID 114613-Methoxybenzoic AcidYield 222.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of diisopropylamine (2.92 ml) and tetrahydrofuran (17.5 ml), at -78°, under nitrogen, was added 1.17 M n-butyllithium (16.3 ml). After stirring for 15 min, a solution of 4-[5-[3-(dimethylcarbamoyl)propyl]-1-propylindol-3-ylmethyl]-3-methoxybenzoic acid (3.8 g) in tetrahydrofuran (50 ml) was added. The reaction was allowed to warmed to -30° and stirred for 45 min. Methyl iodide (2.71 ml) was added and the mixture stirred for 90 min. The reaction was quenched with saturated ammonium chloride (100 ml) and the organic layer was partitioned between ethyl acetate and saturated ammonium chloride. The organic phase was washed (saturated ammonium chloride, water), dried (MgSO4), and evaporated. The residue was dissolved in saturated sodium bicarbonate. The solution was washed with diethyl ether and acidified to pH 2 with 6N hydrochloric acid. The product was extracted into ethyl acetate, and the organic layer was dried (MgSO4) The solvent was evaporated and the residue was triturated with hexane, powderized and vacuum dried at 40° for 18 hr to afford 4-[5-[3-dimethylcarbamoyl)butyl]1-propylindol-3-ylmethyl]-3methoxybenzoic acid (2.95 g, 75%) as a pale pink solid; mp 60.0°-64.0°.

Workup

  1. temperatureto warmed to -30°
  2. stirringstirred for 45 min
  3. stirringthe mixture stirred for 90 min
  4. customThe reaction was quenched with saturated ammonium chloride (100 ml)
  5. customthe organic layer was partitioned between ethyl acetate and saturated ammonium chloride
  6. washThe organic phase was washed (saturated ammonium chloride, water)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. dissolutionThe residue was dissolved in saturated sodium bicarbonate
  10. washThe solution was washed with diethyl ether
  11. extractionThe product was extracted into ethyl acetate
  12. dry with materialthe organic layer was dried (MgSO4) The solvent
  13. customwas evaporated
  14. customthe residue was triturated with hexane
  15. customvacuum dried at 40° for 18 hr

Sources & evidence

ORD record
ord-55c02cc8f16b47f18e57dd9e2ce83938
Source dataset
uspto-grants-1990_01
Patent number
US04894386

Reaction notes

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