4-tert-Butylcyclohexylamine → Methyl 3-bromo-4-{[(4-tert-butylcyclohexyl)amino]methyl}benzoate

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Reaction Steps

To a solution of the product from Example 224 Step B (assume 4.76 mmol) in 5 mL of N,N-dimethylformamide was added 1.02 mL (5.71 mmol) of 4-tert-butylcyclohexylamine and 1.7 mL (9.76 mmol) of N,N-diisopropylethylamine. The resultant mixture was stirred at ambient temperature for 3 hours, diluted with ethyl acetate and the organic layer washed sequentially with three portions of water and one portion of saturated sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (biotage) using 5% ethyl acetate/hexanes as eluent to provide both the cis isomer and the desired trans isomer. 1H NMR (500 MHz, CD3OD) δ 8.18 (s, 1H), 7.97 (d, 1H, J=8 Hz), 7.58 (d, 1H, J=8 Hz), 3.93 (s, 2H), 3.91 (s, 3H), 2.43-2.37 (m, 1H), 2.08-2.01 (m, 2H), 1.85-1.79 (s, 2H), 1.19-4.99 (m, 5H), 0.86 (s, 9H). HPLC/MS (ESI) m/z (M+H)=384.2 (2.47 min.).

Provenance & Evidence