Methyl 4-bromo-2-ethylbenzoate → Methyl 4-cyclopropyl-2-ethylbenzoate

HRID 541368Notes

Reaction equation

HRID 541368 reaction equation
Br[Mg][CH:3]1[CH2:5][CH2:4]1.Br[C:7]1[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([CH2:17][CH3:18])[CH:8]=1>O1CCCC1.[Zn+2].[Br-].[Br-].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:3]1([C:7]2[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:9]([CH2:17][CH3:18])[CH:8]=2)[CH2:5][CH2:4]1

Participants

6

Reactant 2

HCID 53797189Methyl 4-bromo-2-ethylbenzoate2×HCID 178418630HCID 178418630, compound

Product 1

HCID 68288825Methyl 4-cyclopropyl-2-ethylbenzoateYield 89%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of ZnBr2 (37.0 g, 164 mmol, 3.99 equiv) in tetrahydrofuran (150 mL) under nitrogen was added bromo(cyclopropyl)magnesium (3.28 M in THF, 50 mL, 4.00 equiv) dropwise at 0° C. After stirring at 15 minutes at 0° C., the temperature was lowered to −30° C. followed by the dropwise addition of a solution of Pd(dppf)Cl2 (2.00 g, 2.73 mmol, 0.07 equiv) in tetrahydrofuran (50 mL) and a solution of methyl 4-bromo-2-ethylbenzoate (compound 181.2, 10.0 g, 41.1 mmol, 1.00 equiv) in tetrahydrofuran (50 mL). The resulting solution was warmed slowly to 25° C. and stiffed for 15 h, then carefully quenched by slow addition of 100 mL of NH4Cl (aq.sat.). The mixture was extracted with 2×100 mL of ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:30) as eluent to yield 7.50 g (89%) of methyl 4-cyclopropyl-2-ethylbenzoate as a light yellow oil.

Workup

  1. customwas lowered to −30° C.
  2. temperatureThe resulting solution was warmed slowly to 25° C.
  3. waitstiffed for 15 h
  4. customcarefully quenched by slow addition of 100 mL of NH4Cl (aq.sat.)
  5. extractionThe mixture was extracted with 2×100 mL of ethyl acetate
  6. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified

Sources & evidence

ORD record
ord-30866b23805f48daaca59e696164f411
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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