Carbon Dioxide → 4-Isopropoxy-3-methoxybenzoic acid

HRID 1405377Notes

Reaction equation

HRID 1405377 reaction equation
N#N.C([Li])(C)(C)C.Br[C:9]1[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[C:11]([O:19][CH3:20])[CH:10]=1.[C:21](=[O:23])=[O:22]>C1COCC1.O>[CH:16]([O:15][C:12]1[CH:13]=[CH:14][C:9]([C:21]([OH:23])=[O:22])=[CH:10][C:11]=1[O:19][CH3:20])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 280Carbon Dioxide2×HCID 947NitrogenHCID 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 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under a balloon of N2, tert-butyllithium (2.14 mL of 1.6 M, 3.43 mmol) was added drop-wise to a solution of 4-bromo-1-isopropoxy-2-methoxy-benzene (400 mg, 1.63 mmol) in THF (6.0 mL) at −78° C. The mixture was allowed to stir for 1 h at −78° C. before it was added drop-wise to a flask containing CO2 (1.80 g, 40.8 mmol)(solid, dry ice) in THF (2.0 mL). The mixture was allowed to stir for 30 min as it warmed to room temperature (caution: CO2 gas evolution). Water (20 mL) was added and the volatiles were removed under reduced pressure. The resultant aqueous layer was acidified with 1N HCl to pH ˜1-2 and the mixture was extracted with ethyl acetate (3×15 mL). The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated to give 4-isopropoxy-3-methoxy-benzoic acid (≧94% pure, 310 mg, 85%) as a white solid. ESI-MS m/z calc. 210.1, found 210.9 (M+1)+; Retention time: 1.23 min. 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. additionwas added drop-wise to a flask
  2. stirringto stir for 30 min as it
  3. customthe volatiles were removed under reduced pressure
  4. extractionthe mixture was extracted with ethyl acetate (3×15 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-c349cb0bc7b541108ffc07f2656352be
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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