Synthesis
General procedure: p-Aminobenzyl alcohol (1 g, 8.12 mmol, 1 eq.) was dissolved in 80 mL of anhydrous tetrahydrofuran (THF) under nitrogen protection. To this solution was sequentially added N,N-diisopropylethylamine (DIEA, 1.4 mL, 8.12 mmol, 1 eq.) and di-tert-butyl dicarbonate (Boc2O, 1.9 mL, 8.12 mmol, 1 eq.). The reaction mixture was heated to reflux and stirred overnight. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently concentrated under reduced pressure in a rotary evaporator to remove the solvent. The residue was dissolved in ethyl acetate (EtOAc) and the organic layer was washed with 0.1 N hydrochloric acid solution to remove unreacted amine and DIEA.The organic layer was dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated again under reduced pressure. The crude product was purified by silica gel column chromatography with petroleum ether-ethyl acetate (1:1, v/v) as eluent to afford BOC-4-aminobenzyl alcohol (1.85 g, quantitative yield). The structure of the product was confirmed by 1H NMR and 13C NMR: 1H NMR (CDCl3) δ 1.49 (s, 9H), 2.17 (s, 1H), 4.53 (s, 2H), 6.83 (s, 1H), 7.19 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H); 13C NMR (CDCl3) δ 28.28, 64.54, 80.37, 118.49, 127.59, 135.31, 137.46, 152.72.
References
[1] Patent: WO2008/34124, 2008, A2. Location in patent: Page/Page column 72-73
[2] Patent: WO2006/31806, 2006, A2. Location in patent: Page/Page column 99
[3] Research on Chemical Intermediates, 2017, vol. 43, # 3, p. 1355 - 1363
[4] Tetrahedron Letters, 2007, vol. 48, # 51, p. 9044 - 9047
[5] Journal of Medicinal Chemistry, 1992, vol. 35, # 22, p. 4150 - 4159
