Tetrabutylammonium Fluoride → 4-[1,3]Dioxolan-2-yl-2-fluorophenol

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Reaction Steps

To a solution of (4-[1,3]dioxolan-2-yl-2-fluorophenoxy)triisopropylsilane (Example 93. Part B) (105.9 g, approximately 0.311 mol) in THF (1.589 L) add 1.0 M tetrabutylammonium fluoride (TBAF) in THF (311 mL) in a steady stream over 5 min at 23-27° C. without cooling. Stir for 1 hr till the reaction complete by TLC (19:1 heptane/ethyl acetate). Concentrate to a red oil and partition between ether (500 mL) and deionized water (1 L). Separate the layers and extract the aqueous layer with ether (500 mL). Combine the ether layers, wash with brine and dry over sodium sulfate. Filter and concentrate to give the crude product (92.9 g. Dissolve the crude product in dichloromethane and filter through 400 g of silica gel 60. Wash with dichloromethane (3×1 L fractions) and concentrate the combined filtrate to give an impure product. Crystallize from dichloromethane/heptane to give the title compound (29.8 g, 52%). Gas chromatography: retention time 15.96 min (30 m×0.32 mm i.d. DB-1 column, 0.25 micron film thickness; 1.2 mL/min flow rate; 55:1 split ratio; temperature profile: 35° C./3 min, 10° C. temperature increase per min; 250° C./10.5 min). 1H NMR (DMSO-d6) δ 3.84-3.93 (m, 2H, CH2), 3.93-4.04 (m, 2H, CH2), 5.60 (s, 1H, CH), 6.91 (t, 11, ArH), 7.06 (dd, 1H, ArH), 7.15 (dd, 1H, ArH), 10.0 (s, 1H, OH).

Provenance & Evidence