Acetone → 4-Fluoro-alpha-(1-hydroxy-1-methylethyl)benzeneacetic acid

HRID 1416083Notes

Reaction equation

HRID 1416083 reaction equation
[Mg].BrCCBr.C(Cl)(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=[O:19])=[CH:13][CH:12]=1.[CH3:21][C:22]([CH3:24])=[O:23].S(=O)(=O)(O)O>O1CCCC1>[F:10][C:11]1[CH:12]=[CH:13][C:14]([CH:17]([C:22]([OH:23])([CH3:24])[CH3:21])[C:18]([OH:20])=[O:19])=[CH:15][CH:16]=1

Participants

8

Reactant 6

HCID 180AcetoneHCID 1118Sulfuric AcidHCID 63612-ChloropropaneHCID 78391,2-DibromoethaneHCID 98372-(4-Fluorophenyl)acetic acidHCID 5462224Magnesium

Product 1

HCID 109548534-Fluoro-alpha-(1-hydroxy-1-methylethyl)benzeneacetic acidYield 109.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

24.3 g (1.00 mol) of magnesium shavings were suspended in 50 ml of tetrahydrofuran under argon and while stirring in a 1.5 l four-necked sulphonation flask fitted with a reflux condenser, mechanical stirrer, 500 ml dropping funnel, thermometer and a device for inert gasification. After the dropwise addition of 0.5 ml of 1,2-dibromoethane, a solution of 86.4 g (1.10 mol) of isopropyl chloride in 225 ml of tetrahydrofuran was added dropwise within 90 minutes, with the reaction temperature being held at about 30°. The resulting dark grey suspension was stirred at RT for a further 18 hours. Then, a solution of 73.0 g (0.473 mol) of p-fluorophenylacetic acid in 150 ml of tetrahydrofuran was added dropwise to the mixture within 90 minutes while maintaining the temperature at about 25° and thereafter the suspension was heated to 35-40° and stirred at this temperature for a further 1 hour. After cooling 30.0 g (0.516 mol) of acetone were added dropwise at about 25° within 30 minutes and subsequently the mixture was stirred at 35-40° for a further 1 hour. The reaction mixture was treated with 350 ml of 14.2% sulphuric acid while cooling with an ice bath at <30°. The aqueous phase was separated, extracted with 200 ml of tetrahydrofuran and the organic phases were combined and evaporated at 50° on a rotary evaporator. 110 g of crude 2-(p-fluorophenyl)-3-hydroxy-3-methylbutyric acid were obtained as a dark viscous oil.

Workup

  1. customfitted with a reflux condenser, mechanical stirrer
  2. custombeing held at about 30°
  3. stirringThe resulting dark grey suspension was stirred at RT for a further 18 hours
  4. temperaturewhile maintaining the temperature at about 25°
  5. temperaturethe suspension was heated to 35-40°
  6. stirringstirred at this temperature for a further 1 hour
  7. additionwere added dropwise at about 25° within 30 minutes
  8. stirringsubsequently the mixture was stirred at 35-40° for a further 1 hour
  9. temperaturewhile cooling with an ice bath at <30°
  10. customThe aqueous phase was separated
  11. extractionextracted with 200 ml of tetrahydrofuran
  12. customevaporated at 50° on a rotary evaporator

Sources & evidence

ORD record
ord-1f9e2d621d224fdf832e2abf92938066
Source dataset
uspto-grants-1999_06
Patent number
US05910606

Reaction notes

Loading…