Methyl 4-acetylbenzoate → Methyl 4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoate

HRID 1619183Notes

Reaction equation

HRID 1619183 reaction equation
[C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[Si]([C:18]([F:21])([F:20])[F:19])(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[F:19][C:18]([F:21])([F:20])[C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)([OH:3])[CH3:2]

Participants

5

Reactant 3

HCID 137990Methyl 4-acetylbenzoateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride

Product 1

HCID 57892524Methyl 4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 3 L flask containing methyl 4-acetylbenzoate (60 g, 0.34 mol, 1.0 equiv) in 1.0 L THF was added 96.6 g TMS-CF3 (0.68 mol, 2.0 equiv) at 0° C. The solution was allowed to stir for 30 min, followed by the dropwise addition of 680 mL tetrabutylammonium fluoride (1.0M in THF, 0.68 mol, 2.0 equiv) via addition funnel over a period of 3 h. After the addition was complete, the solution was allowed to stir for an additional 30 min and warm to room temperature. The solution was then concentrated down under reduced pressure. Then the mixture was diluted with Sat. NaHCO3 and extracted (4×10% MeOH/CH2Cl2). The organics were combined, dried (MgSO4), and concentrated under reduced pressure. Purification by flash chromatography (SiO2, 15% EtOAc/Hexanes) gave the product as an orange oil.

Workup

  1. additionAfter the addition
  2. stirringto stir for an additional 30 min
  3. concentrationThe solution was then concentrated down under reduced pressure
  4. additionThen the mixture was diluted with Sat. NaHCO3
  5. extractionextracted (4×10% MeOH/CH2Cl2)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography (SiO2, 15% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-1f5fd29d5842427ea46da02cb1d9fbf9
Source dataset
uspto-grants-2014_07
Patent number
US08772296B2

Reaction notes

Loading…