Methyl 4-bromo-2-methylbenzoate → Methyl 4-cyclobutyl-2-methylbenzoate

HRID 541270Notes

Reaction equation

HRID 541270 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>>[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

3

Reactant 2

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

Product 1

HCID 10488418Methyl 4-cyclobutyl-2-methylbenzoate

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 152.1, 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. The mixture was cooled to 0° C. and quenched with water (10 ml). The mixture was diluted with EtOAc (200 ml), washed with water then with brine. The EtOAc layer was dried (Na2SO4), concentrated under reduced pressure, and purified using column (silica gel) chromatography (hexanes:EtOAc 30:1 to 20:1). Yield: 4.1 g, clear oil, 89.1%. 1H NMR (400 MHz, Chloroform-d) 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. temperatureThe mixture was cooled to 0° C.
  4. customquenched with water (10 ml)
  5. additionThe mixture was diluted with EtOAc (200 ml)
  6. washwashed with water
  7. dry with materialThe EtOAc layer was dried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. custompurified

Sources & evidence

ORD record
ord-27c91103071f4ea8a07639c0cc26aa8e
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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