Toluene → Methyl 4-cyclopropyl-2-methylbenzoate

HRID 2069826Notes

Reaction equation

HRID 2069826 reaction equation
[CH:1]1(B(O)O)[CH2:3][CH2:2]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[C:18]([CH3:26])[CH:17]=1.C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.O>[CH:1]1([C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[C:18]([CH3:26])[CH:17]=2)[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 22031226Methyl 4-bromo-2-methylbenzoate

Product 1

HCID 59020660Methyl 4-cyclopropyl-2-methylbenzoateYield 69.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolvent

Procedure

Cyclopropylboronic acid (25.08 g, 292 mmol), anhydrous tribasic potassium phosphate (178.12 g, 839 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.925 g, 14.5 mmol), methyl 4-bromo-2-methylbenzoate (55.93 g, 244 mmol), and 600 mL of toluene were charged into a 1000 mL round bottom flask fitted with a stir bar, septum, and nitrogen inlet. Stirred the mixture rapidly and added 65 mL of water. Sparged the mixture with nitrogen for 30 min. Added tris(dibenzylideneacetone)dipalladium(0) (3.321 g, 3.63 mmol). The reaction mixture was sparged with nitrogen for 15 min. Sealed the flask with a cap and stirred at 90° overnight. Added 150 mL water and allowed to cool to room temperature. Filtered the two phase system through diatomaceous earth to remove the solids and washed the filter cake with EtOAc. Separated the filtrate phases and washed the organic phase with 2×200 mL 5% NaHCO3, 2×200 mL 10% Na2S2O3, and 200 mL brine. Dried the solution over MgSO4 and concentrated in vacuo. Vacuum distilled the residual liquid. Collected the fraction distilling at 108-111°/3 ton to obtain methyl 4-cyclopropyl-2-methylbenzoate as a clear colorless liquid (32.30 g, 170 mmol). 1H NMR (300 MHz, chloroform-d) ppm 0.71-0.80 (m, 2 H) 0.98-1.07 (m, 2 H) 1.83-1.95 (m, 1 H) 2.58 (s, 3 H) 3.87 (s, 3 H) 6.87-6.96 (m, 2 H) 7.83 (d, J=7.91 Hz, 1 H).

Workup

  1. customfitted with a stir bar
  2. customSparged the mixture with nitrogen for 30 min
  3. customThe reaction mixture was sparged with nitrogen for 15 min
  4. customSealed the flask with
  5. customa cap
  6. stirringstirred at 90° overnight
  7. additionAdded 150 mL water
  8. filtrationFiltered the two phase system through diatomaceous earth
  9. customto remove the solids
  10. washwashed the filter cake with EtOAc
  11. customSeparated the filtrate phases
  12. washwashed the organic phase with 2×200 mL 5% NaHCO3, 2×200 mL 10% Na2S2O3, and 200 mL brine
  13. dry with materialDried the solution over MgSO4
  14. concentrationconcentrated in vacuo
  15. distillationVacuum distilled the residual liquid
  16. customCollected the fraction
  17. distillationdistilling at 108-111°/3 ton

Sources & evidence

ORD record
ord-18e15deeef9d4a36a9d5da9dbaf1ee1c
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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