Carbon Dioxide → 4-Isopropoxy-3-methoxybenzoic acid

HRID 72991Notes

Reaction equation

HRID 72991 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([O:17][CH3:18])[CH:8]=1.[C:19](=[O:21])=[O:20].O>C1COCC1>[CH:14]([O:13][C:10]1[CH:11]=[CH:12][C:7]([C:19]([OH:21])=[O:20])=[CH:8][C:9]=1[O:17][CH3:18])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 962WaterHCID 11149245Benzene, 4-bromo-2-methoxy-1-(1-methylethoxy)-HCID 178418306HCID 178418306, compound

Product 1

HCID 20639154-Isopropoxy-3-methoxybenzoic acidYield 90.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under an atmosphere of nitrogen, tert-butyllithium (2.14 mL of 1.6 M in toluene, 3.42 mmol) was added dropwise to a solution of 4-bromo-1-isopropoxy-2-methoxy-benzene (400 mg, 1.63 mmol) in THF (6 mL) at −78° C. The reaction mixture was allowed to stir for 1 hour at −78° C., then added dropwise to a flask containing CO2 (1.8 g, 40.8 mmol) (solid, dry ice) in THF (2 mL). The reaction mixture was allowed to stir for 30 minutes warming to room temperature. Water (20 mL) was added to the reaction mixture and the volatiles were removed in vacuo. The resultant aqueous layer was acidified with 1N HCl solution to pH 1 and was extracted with ethyl acetate (3×15 mL). The organics were separated and the combined organics were washed with brine solution, dried over sodium sulfate, filtered and concentrated in vacuo to give 4-isopropoxy-3-methoxy-benzoic acid (310 mg, 85%) as a white solid. ESI-MS m/z calc. 210.1. Found 211.1 (M+1)+; Retention time: 1.23 minutes (3 min run). 1H NMR (400 MHz, DMSO) δ 12.63 (s, 1H), 7.53 (dd, J=8.4, 2.0 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 7.04 (d, J=8.7 Hz, 1H), 4.67 (dt, J=12.1, 6.0 Hz, 1H), 3.78 (s, 3H), 1.28 (d, J=6.0 Hz, 6H).

Workup

  1. additionadded dropwise to a flask
  2. stirringto stir for 30 minutes
  3. temperaturewarming to room temperature
  4. customthe volatiles were removed in vacuo
  5. extractionwas extracted with ethyl acetate (3×15 mL)
  6. customThe organics were separated
  7. washthe combined organics were washed with brine solution
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1a52ebea6e5b4c628eae640d960252cf
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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