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

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Reaction Steps

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.

Provenance & Evidence