P-Anisidine → Methyl 3-(4-methoxyanilino)benzoate

HRID 2180359Notes

Reaction equation

HRID 2180359 reaction equation
CC([O-])(C)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:15][O:16][C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20](Br)[CH:19]=1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([NH2:34])=[CH:30][CH:29]=1>COCCOC.CCOCC.CCCCCCCCCCCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:15][O:16][C:17](=[O:25])[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([NH:34][C:31]2[CH:32]=[CH:33][C:28]([O:27][CH3:26])=[CH:29][CH:30]=2)[CH:19]=1

Participants

9

Reactant 4

HCID 7732P-AnisidineHCID 12070Methyl 3-bromobenzoateHCID 62657Potassium Phosphate, TribasicHCID 23676156Sodium t-butoxide

Product 1

HCID 22492538Methyl 3-(4-methoxyanilino)benzoateYield 4.7%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolventHCID 8182DodecaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of Pd2(dba)3 [92 mg, 0.1 mmol (4.6 mg, 0.005 mmol, 2 mol % Pd per reaction)], ligand 1 (see FIG. 1) [168 mg, 0.4 mmol (8.4 mg, 0.02 mmol, 4 mol % per reaction)] and NaOt-Bu [40 mg, 0.4 mmol (2 mg, 0.02 mmol, 4 mol % per reaction)] were stirred in 10 mL DME (anhy). After 10 minutes, 0.5 mL of the solution was added via syringe to a test tube containing (under an Argon atmosphere) K3PO4 (148 mg, 0.7 mmol), methyl-3-bromo-benzoate (107 mg, 0.5 mmol), and p-anisidine (74 mg, 0.6 mmol). The test tube was capped (with a proper cap-no rubber septa) and heated at 100° C. for 18 hours. The reaction mixture was allowed to cool to r.t., diluted with ether and dodecane was added as an internal standard. The reaction mixture was purified by preparatory TLC (EtOAc/hexanes as the eluent) to yield 6 mg of the desired product (which was used for calibration with the internal standard). The GC yield was calculated to be 12%.

Workup

  1. customThe test tube was capped (with a proper cap-no rubber septa) and
  2. temperatureto cool to r.t.
  3. additionwas added as an internal standard
  4. customThe reaction mixture was purified by preparatory TLC (EtOAc/hexanes as the eluent)

Sources & evidence

ORD record
ord-2452aa7879084bd6afcade621c7f8e6e
Source dataset
uspto-grants-2005_05
Patent number
US06888029B2

Reaction notes

Loading…