Cesium carbonate → 4-(5,8,8-Trimethyl-7,8-dihydro-naphthalen-2-yl-amino)-benzoic acid ethyl ester

HRID 1795599Notes

Reaction equation

HRID 1795599 reaction equation
[CH3:1][C:2]1[C:3]2[CH:4]=[CH:5][C:6]([NH2:14])=[CH:7][C:8]=2[C:9]([CH3:13])([CH3:12])[CH2:10][CH:11]=1.Br[C:16]1[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=C(C3C4C(=CC=CC=4)C=CC=3)C3C(C=2)=CC=CC=3)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.O.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]>[CH2:23]([O:22][C:20](=[O:21])[C:19]1[CH:25]=[CH:26][C:16]([NH:14][C:6]2[CH:5]=[CH:4][C:3]3[C:2]([CH3:1])=[CH:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]=3[CH:7]=2)=[CH:17][CH:18]=1)[CH3:24]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 22043Ethyl 4-bromobenzoateHCID 18630801Bis(diphenylphosphino)-1,1'-binaphthylHCID 222183455,8,8-Trimethyl-7,8-dihydro-naphthalen-2-ylamine2×

Product 1

HCID 210243674-(5,8,8-Trimethyl-7,8-dihydro-naphthalen-2-yl-amino)-benzoic acid ethyl ester

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

General Procedure L To a solution of 5,8,8-trimethyl-7,8-dihydro-naphthalen-2-yl-amine (Compound 64, 0.33 g, 1.8 mmol) and ethyl 4-bromobenzoate (0.52 g, 2.3 mmol) in 10.0 mL of toluene while stirring under argon were added cesium carbonate (0.89 g, 2.7 mmol), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 33 mg, 0.04 mmol) and bis(diphenylphosphino)-1,1′-binaphthyl (BINAP, 47 mg, 0.08 mmol) consecutively. The reaction was then heated at 100° C. for 24 h. The reaction was then cooled to room temperature, diluted with water and extracted 2 times with ethyl ether. The combined organic extracts were washed with brine, dried over MgSO4, filtered, and the solvents were removed in vacuo. The crude product was purified by silica gel chromatography (10% ethyl acetate in hexanes) to give the title compound as a yellow solid.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. extractionextracted 2 times with ethyl ether
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvents were removed in vacuo
  7. customThe crude product was purified by silica gel chromatography (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-079a93512d444eb4a575adc250df4e07
Source dataset
uspto-grants-2006_04
Patent number
US07026487B2

Reaction notes

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