Azobisisobutyronitrile → Ethyl 4-(bromomethyl)-3-chloro-5-fluorobenzoate

HRID 83891Notes

Reaction equation

HRID 83891 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([F:14])[C:12]=1[CH3:13])[C:5]([O:7][CH2:8][CH3:9])=[O:6].C1C(=O)N([Br:22])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl.O>[Br:22][CH2:13][C:12]1[C:11]([F:14])=[CH:10][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:3][C:2]=1[Cl:1]

Participants

6

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 66740540Ethyl 3-chloro-5-fluoro-4-methylbenzoate

Product 1

HCID 66740817Ethyl 4-(bromomethyl)-3-chloro-5-fluorobenzoateYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 3-chloro-5-fluoro-4-methylbenzoate (5.3 g, 24.46 mmol) in CCl4 (100 mL) was added NBS (4.79 g, 26.91 mmol) followed by AIBN (0.4 g, 2.45 mmol). The reaction mixture was heated at 80° C. overnight. After cooling, the reaction mixture was diluted with H2O and washed with DCM (2×). The combined extracts were dried (Na2SO4), concentrated and purified by flash chromatography (12% EtOAc/Hex) to yield ethyl 4-(bromomethyl)-3-chloro-5-fluorobenzoate (3.53 g, 49%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 7.96-7.85 (m, 1H), 7.83 (dd, J=9.6, 1.5 Hz, 1H), 4.80 (t, J=5.7 Hz, 2H), 4.41 (q, J=7.1 Hz, 2H), 3.47 (s, 1H), 1.47-1.30 (m, 3H).

Workup

  1. temperatureAfter cooling
  2. washwashed with DCM (2×)
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified by flash chromatography (12% EtOAc/Hex)

Sources & evidence

ORD record
ord-d55fe2e45505430dbc9f5c9723c8918f
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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