Ammonium Chloride → Methyl 3-[2-(4-fluorophenyl)-2-oxoethyl]benzoate

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Reaction Steps

To a solution of the TMS cyanohydrin from Example 1, Step 1 (3.70 g, 16.6 mmol) in THF (40 mL) under N2 at −78° C. was added slowly a solution of LHMDS (18.2 mL, 18.2 mmol, 1.0 M/THF). After 15 min. at −78° C., a solution of methyl 3-(bromomethyl)benzoate (3.99 g, 17.4 mmol) in THF (20 mL) was added via double-tipped needle. The reaction was allowed to warm slowly to r.t. over 1 h. and was then stirred at r.t. for 2.5 h. Bu4NF (33 mL, 33 mmol, 1M/THF) was then added and the mixture was stirred for 1 h. Saturated NH4Cl (20 mL) was then added and the product was extracted with EtOAc. The organic phase was washed with H2O and brine, and was then dried (MgSO4), filtered, and evaporated. The residue was stirred vigourously with 1:5 Et2O:hexane (50 mL) for 1 h, and the product was then obtained by filtration. This material was dissolved in CH2Cl2 and filtered through a plug of silica gel, washing with CH2Cl2. After removal of solvent, a pale yellow solid (3.4 g) was obtained.

Provenance & Evidence