Dichloromethane → Methyl 4-isopropyl-2-methylbenzoate

HRID 541316Notes

Reaction equation

HRID 541316 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:12])[CH:3]=1.[CH2:13](Cl)Cl.O1[CH2:21][CH2:20]OCC1>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]>[CH:20]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:12])[CH:3]=1)([CH3:21])[CH3:13]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 312751,4-DioxaneHCID 22031226Methyl 4-bromo-2-methylbenzoate2×

Product 1

HCID 10702909Methyl 4-isopropyl-2-methylbenzoateYield 96%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

A dried round bottom flask with stir bar was purged with nitrogen and charged with diisopropyl zinc (25 mL of a 1 M solution in THF, 25 mmol, 2.0 equiv). Methyl 4-bromo-2-methylbenzoate (compound 152.1, 2.86 g, 12.5 mmol, 1.0 equiv) in 1,4-dioxane (25 mL) was added followed by addition of Pd(dppf)2Cl2.DCM (1.02 g, 1.25 mmol, 0.1 equiv) (exothermic upon catalyst addition). The system was purged with additional nitrogen then argon and heated to 100° C. for 4 hours then stirred at room temperature for 12 hours. The mixture was carefully quenched with 1M HCl (ag., 12 mL) (some bubbling) and then diluted with water (100 mL) and ethyl acetate (150 mL) and mixed. The mixture was filtered through celite and washed with water and ethyl acetate (2×25 mL each). The layers were separated and the aqueous was extracted with addition ethyl acetate (50 mL). The combined organics were washed with brine (50 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexanes to 6% ethyl acetate) to obtain the title compound as a colorless oil (2.31 g, 96%). 1H NMR (400 MHz, CDCl3): δ 7.86 (d with fine str, J=8.8 Hz, 1H), 7.12-7.07 (m, 2H), 3.87 (s, 3H), 2.90 (septet, J=6.8 Hz, 1H), 2.59 (s, 3H), 1.25 (d, J=6.8 Hz, 6H).

Workup

  1. customwas purged with nitrogen
  2. additioncharged with diisopropyl zinc (25 mL of a 1 M solution in THF, 25 mmol, 2.0 equiv)
  3. customThe system was purged with additional nitrogen
  4. stirringthen stirred at room temperature for 12 hours
  5. customThe mixture was carefully quenched with 1M HCl (ag., 12 mL) (some bubbling) and
  6. additionthen diluted with water (100 mL) and ethyl acetate (150 mL)
  7. additionmixed
  8. filtrationThe mixture was filtered through celite
  9. washwashed with water and ethyl acetate (2×25 mL each)
  10. customThe layers were separated
  11. extractionthe aqueous was extracted with addition ethyl acetate (50 mL)
  12. washThe combined organics were washed with brine (50 mL)
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated under reduced pressure
  15. customThe crude product was purified by silica gel column chromatography (hexanes to 6% ethyl acetate)

Sources & evidence

ORD record
ord-26be84e55375475b863d9f77026dd526
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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