3-Fluoro-4-hydroxybenzoic acid → (S)-2-methylbutyl 3-fluoro-4-hydroxybenzoate

HRID 654422Notes

Reaction equation

HRID 654422 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[OH:11])[C:5]([OH:7])=[O:6].[CH3:12][C@@H:13]([CH2:16][CH3:17])[CH2:14]O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[OH:11])[C:5]([O:7][CH2:12][C@@H:13]([CH3:14])[CH2:16][CH3:17])=[O:6]

Participants

5

Reactant 3

HCID 1604563-Fluoro-4-hydroxybenzoic acidHCID 521998p-Toluenesulfonic acid monohydrateHCID 2723602(S)-2-methyl-1-butanol

Product 1

HCID 54464410(S)-2-methylbutyl 3-fluoro-4-hydroxybenzoateYield 66%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

In a 250-ml, round-bottomed flask equipped with a heating mantle, magnetic stirrer, condenser and Dean Stark trap, were placed 2.5 g (16.0 mmol) of 3-fluoro-4-hydroxybenzoic acid, ten g (113.4 mmol) of (S)-2-methyl-1-butanol, 0.347 g of p-toluenesulfonic acid monohydrate and 100 mls of benzene. The reaction mixture was stirred overnight under reflux. The reaction mixture was extracted using saturated aqueous sodium bicarbonate. The organic phase was dried over sodium sulfate, filtered through cotton and evaporated to an oil. The product was purified by flash chromatography on silica gel with 3% diethyl ether in dichloromethane. Fractions containing the desired product were combined and evaporated to a pale-yellow oil. Analysis by NMR showed that considerable starting alcohol remained. The oil was placed under vacuum (at 70° C.) for two days. No alcohol was shown by gas chromatography to be present. The desired product was obtained in the amount of 2.39 g (66% yield) and had the following structure. ##STR44##

Workup

  1. customIn a 250-ml, round-bottomed flask equipped with a heating mantle, magnetic stirrer, condenser and Dean Stark trap
  2. temperatureunder reflux
  3. extractionThe reaction mixture was extracted
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered through cotton
  6. customevaporated to an oil
  7. customThe product was purified by flash chromatography on silica gel with 3% diethyl ether in dichloromethane
  8. additionFractions containing the desired product
  9. customevaporated to a pale-yellow oil
  10. waitThe oil was placed under vacuum (at 70° C.) for two days

Sources & evidence

ORD record
ord-bc471de5db10476aaa32b4f917de1ade
Source dataset
uspto-grants-1992_07
Patent number
US05132041

Reaction notes

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