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

HRID 79008Notes

Reaction equation

HRID 79008 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].CN(C=O)C.[C:17](O)([CH3:20])([CH3:19])[CH3:18].N1C=CC=CC=1>ClCCl.C1CCCCC1.C(Cl)(=O)C(Cl)=O.C(OCC)(=O)C>[C:17]([O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([F:11])=[CH:10][C:2]=1[Br:1])([CH3:20])([CH3:19])[CH3:18]

Participants

9

Reactant 4

HCID 1049PyridineHCID 6228DimethylformamideHCID 6386tert-ButanolHCID 12681692-Bromo-4-fluorobenzoic acid

Product 1

HCID 26986095tert-Butyl 2-bromo-4-fluorobenzoateYield 42.5%

Reagents, catalysts & solvents 4

HCID 65578Oxalyl chlorideCatalystHCID 6344DichloromethaneSolvent3×HCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2-bromo-4-fluoro-benzoic acid (28.5 g, 0.13 mol) in dichloromethane (500 mL) at room temperature was added oxalyl chloride (11.35 mL, 0.26 mmol) followed by DMF (0.05 mL, catalytic, CARE vigorous gas evolution) and the reaction mixture stirred for 3 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in DCM (500 mL) before treatment with a solution of tert-butanol (28.5 g, 0.26 mol) and pyridine (20.5 g, 0.26 mol). The resultant mixture was stirred at room temperature for 3 days before it was diluted with DCM and washed (1M aqueous sodium hydroxide, water, 0.1M aqueous HCl, water) dried (Na2SO4) filtered and concentrated in vacuo to give a yellow oil. The crude oil was subjected to flash chromatography (Si—PPC, gradient 0 to 20% ethyl acetate in cyclohexane) to give the title compound as a colourless oil (15.2 g, 42%). 1H NMR (CDCl3, 400 MHz) 7.76-7.73 (1H, m), 7.37 (1H, dd, J=8.36, 2.53 Hz), 7.05 (1H, ddd, J=8.70, 7.73, 2.53 Hz), 1.60 (9 H, s).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. washwashed (1M aqueous sodium hydroxide, water, 0.1M aqueous HCl, water)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a yellow oil

Sources & evidence

ORD record
ord-0bab7a610e214b8d9b0c775f9025ab09
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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