Methyl 4-bromobenzoate → Methyl 4-cyclobutylbenzoate

HRID 541284Notes

Reaction equation

HRID 541284 reaction equation
Br[Mg][CH:3]1[CH2:6][CH2:5][CH2:4]1.Br[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][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:3]1([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 2

HCID 12081Methyl 4-bromobenzoateHCID 178419648HCID 178419648, compound

Product 1

HCID 68288440Methyl 4-cyclobutylbenzoate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
-40 °C

Procedure

To a stirred mixture of ZnBr2 (83.0 g, 368.53 mmol, 4.00 equiv) in THF (500 mL) under nitrogen at 0° C. was added a solution of bromo(cyclobutyl)magnesium (242 mL, 364 mmol, 1.5 M in THF) dropwise during 20 min. To the resulting mixture were added Pd(dppf)Cl2 (2.00 g, 0.10 equiv) and methyl 4-bromobenzoate (20 g, 93.00 mmol, 1.00 equiv) at −40° C. The resulting mixture was stirred at −40° C. for 1 h under nitrogen, and then carefully quenched with 500 mL of NH4Cl(aq., sat.). The mixture was extracted with 3×500 mL of ethyl acetate. The combined organic layers were washed with 3×500 mL of brine, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure to yield 18.0 g (crude) of the title compound as a light yellow oil.

Workup

  1. customcarefully quenched with 500 mL of NH4Cl(aq., sat.)
  2. extractionThe mixture was extracted with 3×500 mL of ethyl acetate
  3. washThe combined organic layers were washed with 3×500 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cf1afbe06ec44337bacf0c97d309786a
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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