4-Nitrobenzonitrile → Benzonitrile, 4-(2,2,2-trifluoro-1,1-dimethylethoxy)-

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Reaction Steps

Add 2-trifluoromethyl-2-propanol (3.4 g, 27 mmol) slowly to a slurry of sodium hydride (0.6 g, 60% in mineral oil, washed with hexane) in HMPA (5 mL) under nitrogen. Stir the slurry for 15 min and add a solution of 4-nitrobenzonitrile (2.0 g, 13.5 mmol) in HMPA (10 mL). Stir the resulting purple slurry at ambient temperature for 16 h, dilute with diethyl ether (100 mL) and wash with 5% aqueous HCl (30 mL). Separate the layers and extract the aqueous layer with diethyl ether (2×50 mL). Combine the organic extracts and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1) to obtain the desired intermediate (780 mg, 25%). GC-MS m/z: 229 (M+).

Provenance & Evidence