Methyl 4-bromobenzoate → Methyl 4-cyclobutylbenzoate
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]1Participants
6
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -40 °C
Procedure
To a stirred mixture of ZnBr2 (83.0 g, 369 mmol) in THF (500 mL) under nitrogen at 0° C. was added a solution of bromo(cyclobutyl)magnesium (242 mL, 363 mmol, 1.5 M in THF) dropwise over 20 min. The resulting mixture was cooled to −40° C. and Pd(dppf)Cl2 (2.00 g, 2.73 mmol) and methyl 4-bromobenzoate (20.0 g, 93.0 mmol) were added. The resulting mixture was stirred at -40° C. for 1 h under nitrogen, and then carefully quenched with saturated aqueous NH4Cl (500 mL). The mixture was extracted with ethyl acetate (3×500 mL) and the combined organic layers were washed with brine (3×500 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to yield the title compound as a light yellow oil (18.0 g, crude).
Workup
- customcarefully quenched with saturated aqueous NH4Cl (500 mL)
- extractionThe mixture was extracted with ethyl acetate (3×500 mL)
- washthe combined organic layers were washed with brine (3×500 mL)
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-cc5098f693a64f0fb372efbbe97aacbc
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09428502B2
Reaction notes
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