4-Bromo-3-methoxybenzoic acid → 4-Ethyl-3-methoxybenzoic acid

HRID 1908101Notes

Reaction equation

HRID 1908101 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[O:11][CH3:12].[Zn](CC)[CH2:14][CH3:15]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:14]([C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[O:11][CH3:12])[CH3:15]

Participants

5

Reactant 2

HCID 162158674-Bromo-3-methoxybenzoic acidHCID 178418750HCID 178418750, compound

Product 1

HCID 299406594-Ethyl-3-methoxybenzoic acid

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-bromo-3-methoxy-benzoic acid (2.49 g, 10.9 mmol) and Pd(dppf)Cl2 (158 mg, 0.216 mmol) were stirred in dioxane (25 mL) and Et2Zn (22 mL, 1M in hexanes, 22 mmol) was added. The reaction mixture was heated at 70° C. for 1 h. The mixture was cooled to room temperature and was quenched with MeOH (1.1 mL). The solution was diluted with ethyl acetate (20 mL) and was washed with 1N HCl (10 mL). The combined organics were washed with brine, dried over sodium sulfate and evaporated to dryness to give 4-ethyl-3-methoxybenzoic acid. ESI-MS m/z calc. 180.1. found 179.1 (M−1)−; Retention time: 1.77 minutes (3 min run).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customwas quenched with MeOH (1.1 mL)
  3. additionThe solution was diluted with ethyl acetate (20 mL)
  4. washwas washed with 1N HCl (10 mL)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-aab18bdac078475d82f5b663cbb33660
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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