Dimethylformamide → tert-Butyl 4-bromo-2-fluorobenzoate

HRID 2102923Notes

Reaction equation

HRID 2102923 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([F:11])[CH:3]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[C:23](O)([CH3:26])([CH3:25])[CH3:24]>C1COCC1.C(Cl)Cl.N1C=CC=CC=1>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:7])=[C:4]([F:11])[CH:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 6386tert-ButanolHCID 65578Oxalyl chlorideHCID 3026814-Bromo-2-fluorobenzoic acid

Product 1

HCID 46738774tert-Butyl 4-bromo-2-fluorobenzoateYield 45%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-bromo-2-fluorobenzoic acid (3.0 g, 0.014 mol) in THF (50 mL) at 0° C. was added DMF (0.1 mL) and oxalyl chloride (1.5 mL, 0.018 mol). The mixture was stirred at 0° C. for 1 h and then warmed to rt. The solvent was removed under reduced pressure. The obtained acid chloride was added to a mixture of tert-butyl alcohol (5.0 g, 0.067 mol), pyridine (10 mL), and CH2Cl2 (50 mL) at 0° C. The mixture was stirred at rt for 3 h, and then at 50° C. overnight. The mixture was washed with water, 2 N NaOH, and brine, dried (MgSO4), and concentrated under vacuum. The residue was purified by column to give a colorless oil (1.5 g, 45%).

Workup

  1. temperaturewarmed to rt
  2. customThe solvent was removed under reduced pressure
  3. stirringThe mixture was stirred at rt for 3 h
  4. customat 50° C.
  5. customovernight
  6. washThe mixture was washed with water, 2 N NaOH, and brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by column

Sources & evidence

ORD record
ord-560df851548a42419981ab90be556b94
Source dataset
uspto-grants-2009_08
Patent number
US07576099B2

Reaction notes

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