tert-Butanol → Tert-butyl 2-fluoro-4-nitrobenzoate

HRID 56619

Reaction equation

HRID 56619 reaction equation
[C:1]([OH:5])([CH3:4])([CH3:3])[CH3:2].[F:6][C:7]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:8]=1[C:9](O)=[O:10].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>N1C=CC=CC=1>[F:6][C:7]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:8]=1[C:9]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:10]

Participants

5

Reactant 3

HCID 6386tert-Butanol2×HCID 73974-Toluenesulfonyl chlorideHCID 3026792-Fluoro-4-nitrobenzoic acid

Product 1

HCID 10243388Tert-butyl 2-fluoro-4-nitrobenzoate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

At 0° C., 0.258 ml (2.7 mmol, 1.0 eq.) of tert-butanol was added to a solution of 500 mg (2.7 mmol) of 2-fluoro-4-nitrobenzoic acid and 1.03 g (5.4 mmol, 2.0 eq.) of para-toluenesulphonyl chloride in 5.4 ml of pyridine, the mixture was stirred for 60 min and a further 0.258 ml (2.7 mmol, 1.0 eq.) of tert-butanol was added. The reaction mixture was stirred for another 18 h and concentrated under reduced pressure. Saturated aqueous sodium bicarbonate solution and ethyl acetate were added to the residue. After phase separation, the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude product was then purified by normal phase chromatography (mobile phase: cyclohexane/ethyl acetate 14%-20% mixtures). Yield: 524 mg (75% of theory).

Workup

  1. stirringThe reaction mixture was stirred for another 18 h
  2. concentrationconcentrated under reduced pressure
  3. additionSaturated aqueous sodium bicarbonate solution and ethyl acetate were added to the residue
  4. customAfter phase separation
  5. extractionthe aqueous phase was extracted with ethyl acetate
  6. washThe combined organic phases were washed with saturated aqueous sodium chloride solution
  7. dry with materialdried (sodium sulphate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was then purified by normal phase chromatography (mobile phase: cyclohexane/ethyl acetate 14%-20% mixtures)

Sources & evidence

ORD record
ord-78ddad5c1bcd40f2b81e8242c0e831a8
Source dataset
uspto-grants-2016_09
Patent number
US09434690B2

Linked notes

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