Acetone → 3-(1-Hydroxy-1-methylethyl)-benzoic acid

HRID 1055699Notes

Reaction equation

HRID 1055699 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16]([OH:18])=[O:17].[CH3:22][C:23]([CH3:25])=[O:24]>C1COCC1.[Cl-].[NH4+].O>[OH:24][C:23]([C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=1)[C:16]([OH:18])=[O:17])([CH3:25])[CH3:22]

Participants

8

Reactant 4

HCID 180AcetoneHCID 8058HexaneHCID 114563-Bromobenzoic acidHCID 178418339Butyllithium

Product 1

HCID 81671183-(1-Hydroxy-1-methylethyl)-benzoic acid

Reagents, catalysts & solvents 3

HCID 25517Ammonium ChlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Under argon and at −78° C., 4 ml (9.95 mmol) of a 2.5 M solution of n-butyllithium in a hexane fraction were added dropwise to a solution of 1.0 g (4.97 mmol) of 3-bromobenzoic acid in 20 ml of anhydrous THF. After 20 min, 730 μl (9.95 mmol) of acetone were added dropwise at the same temperature. The reaction mixture was stirred at −78° C. for a further hour and then allowed to warm to RT over the course of about 1 h. The reaction mixture was then hydrolysed by careful addition of a few drops of saturated aqueous ammonium chloride solution. The mixture was diluted with 200 ml of water and extracted five times with in each case about 25 ml of ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and freed from the solvent on a rotary evaporator. The residue obtained was purified in four portions by preparative HPLC (Method 36). Pooling of the product fractions, evaporation and drying under high vacuum gave 356 mg (39% of theory) of the title compound.

Workup

  1. temperatureto warm to RT over the course of about 1 h
  2. extractionextracted five times with in each case about 25 ml of ethyl acetate
  3. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customfreed from the solvent on a rotary evaporator
  7. customThe residue obtained
  8. customwas purified in four portions by preparative HPLC (Method 36)
  9. customPooling of the product fractions, evaporation
  10. customdrying under high vacuum

Sources & evidence

ORD record
ord-aa6a505122634c419fe8ec75ebe7713d
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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