Dichloromethane → Methyl 4-cyclobutyl-2-methylbenzoate

HRID 1487840Notes

Reaction equation

HRID 1487840 reaction equation
[Br-].[CH:2]1([Zn+])[CH2:5][CH2:4][CH2:3]1.Br[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:18])[CH:9]=1.C(Cl)Cl>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:2]1([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([CH3:18])[CH:9]=2)[CH2:5][CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 22031226Methyl 4-bromo-2-methylbenzoate2×HCID 178419766HCID 178419766, compound

Product 1

HCID 10488418Methyl 4-cyclobutyl-2-methylbenzoateYield 89%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

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 4-bromo-2-methylbenzoate (compound 6.1, 5.2 g, 22.7 mmol) and PdCl2(dppf).CH2Cl2 (1.85 g, 2.27 mmol). The mixture was degassed and the flask was filled with argon through a balloon. The mixture was heated at 65° C. under argon for 24 hours, then cooled to 0° C. and carefully quenched with water (10 mL). The mixture was diluted with EtOAc (200 mL) and washed with water then brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1) to yield the title compound as a clear oil (4.1 g, 89%). 1H NMR (400 MHz, CDCl3) δ 7.86 (d, 1H), 7.12-7.02 (m, 2H), 3.88 (s, 3H), 3.59-3.48 (m, 1H), 2.59 (s, 3H), 2.35 (m, 2H), 2.22-1.96 (m, 3H), 1.86-1.84 (m, 1H).

Workup

  1. customThe mixture was degassed
  2. additionthe flask was filled with argon through a balloon
  3. temperaturecooled to 0° C.
  4. customcarefully quenched with water (10 mL)
  5. additionThe mixture was diluted with EtOAc (200 mL)
  6. washwashed with water
  7. dry with materialbrine, dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified

Sources & evidence

ORD record
ord-29747624efa141f0925b7c002b8bfead
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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