Methyl 2-bromo-4-methylbenzoate → Methyl 2-cyclobutyl-4-methylbenzoate
Reaction equation
[Br-].[CH:2]1([Zn+])[CH2:5][CH2:4][CH2:3]1.Br[C:8]1[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:9]=1[C:10]([O:12][CH3:13])=[O:11]>>[CH:2]1([C:8]2[CH:17]=[C:16]([CH3:18])[CH:15]=[CH:14][C:9]=2[C:10]([O:12][CH3:13])=[O:11])[CH2:5][CH2:4][CH2:3]1Participants
Conditions
- Temperature
- 65 °C
Procedure
Cyclobutylzinc(II) bromide (50 mL, 0.5 M in THF, 25.0 mmol) was added to a mixture of methyl 2-bromo-4-methylbenzoate (compound 89.1, 5.0 g, 21.8 mmol) and PdCl2(dppf)CH2Cl2 (1.78 g, 2.20 mmol). The mixture was degassed with argon, then heated at 65° C. under argon for 24 hours. The mixture was cooled to 0° C., then carefully quenched with water (10 mL). The mixture was diluted with EtOAc (200 mL) and washed with water then brine. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1) to yield 3.6 g (81%) of the title compound. 1H NMR (400 MHz, Chloroform-d) δ 7.68 (d, 1H), 7.23-7.17 (s, 1H), 7.03 (d, 1H), 4.16 (m, 1H), 3.86 (s, 3H), 2.39 (s, 3H), 2.34 (m, 2H), 2.16-1.96 (m, 3H), 1.80 (m, 1H).
Workup
- customThe mixture was degassed with argon
- temperatureThe mixture was cooled to 0° C.
- customcarefully quenched with water (10 mL)
- additionThe mixture was diluted with EtOAc (200 mL)
- washwashed with water
- dry with materialThe organic layer was dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1)
Sources & evidence
- ORD record
- ord-72d1b97fbd6f4409b8a9241ba2bdd1f8
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09428502B2
Reaction notes
Loading…