Methyl 4-bromo-2-ethylbenzoate → Methyl 4-cyclobutyl-2-ethylbenzoate

HRID 541298Notes

Reaction equation

HRID 541298 reaction equation
[CH:1]1([Mg]Br)[CH2:4][CH2:3][CH2:2]1.Br[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH2:18][CH3:19])[CH:9]=1>C1COCC1.[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:1]1([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH2:18][CH3:19])[CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 53797189Methyl 4-bromo-2-ethylbenzoate2×HCID 178419648HCID 178419648, compound

Product 1

HCID 68288811Methyl 4-cyclobutyl-2-ethylbenzoateYield 99%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of ZnBr2 (33.5 g, 149 mmol, 4.00 equiv) in THF (350 mL) under nitrogen at 0° C. was added dropwise a solution of cyclobutylmagnesium bromide (148 mmol in 50 mL THF). After stirring at 0° C. for 0.5 h, the temperature was lowered to −78° C. and Pd(dppf)Cl2 (2.00 g, 2.73 mmol, 0.07 equiv) was added followed by the addition of a solution of methyl 4-bromo-2-ethylbenzoate (compound 181.2, 9.00 g, 37.0 mmol, 1.00 equiv) in tetrahydrofuran (10 mL) dropwise at the same temperature. The reaction mixture was slowly allowed to reach ambient temperature and then stirred overnight. The reaction was carefully quenched with a saturated NH4Cl aqueous solution (100 mL). The resulting mixture was extracted with 500 mL of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50) to furnish 8.00 g (99%) of the desired product as a light yellow oil.

Workup

  1. customwas lowered to −78° C.
  2. customto reach ambient temperature
  3. stirringstirred overnight
  4. customThe reaction was carefully quenched with a saturated NH4Cl aqueous solution (100 mL)
  5. extractionThe resulting mixture was extracted with 500 mL of ethyl acetate
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:50)

Sources & evidence

ORD record
ord-c1e9626131934eecb11d9b16e46e498e
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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