Synthesis
General procedure for the synthesis of tert-butyl 4-formylbenzylcarbamate from tert-butyl 4-(hydroxymethyl)benzylcarbamate: tert-butyl 4-(hydroxymethyl)benzylcarbamate (2.20 g, 9.2 mmol) was dissolved in dichloromethane (DCM, 100 ml), and manganese dioxide (MnO2, 8.18 g, 92 mmol, 10 equiv) was added. The resulting suspension was stirred at room temperature for 3 hours. After completion of the reaction, the reaction mixture was filtered through diatomaceous earth to remove insoluble impurities. The filtrate was concentrated under reduced pressure to afford tert-butyl 4-formylbenzylcarbamate as a white solid (2.18 g, 9.2 mmol, 100% yield). Thin layer chromatography (TLC) analysis showed Rf = 0.62 (Expander: DCM/ethyl acetate, 9:1). Infrared spectroscopy (IR) showed characteristic absorption peaks. Nuclear magnetic resonance hydrogen spectrum (1H NMR, 300 MHz, CDCl3) δ = 10.0 (s, 1H, CHO), 7.85 (d, J = 8.1 Hz, 2H, ArCH adjacent to CHO), 7.45 (d, J = 8.1 Hz, 2H, ArCH adjacent to CH2NHBoc), 4.99 (bs. 1H, NHBoc), 4.40 (d, J = 5.7 Hz, 2H, CH2NHBoc), 1.47 (s, 9H, C(CH3)3). Nuclear magnetic resonance carbon spectrum (13C NMR, 75 MHz, CDCl3) δ = 191.9 (CHO), 155.9 (CO), 145.9 (ArCCH2NHBoc), 135.5 (ArCCHO), 130.1 (ArCH adjacent to CHO), 127.6 (ArCH adjacent to CH2NHBoc), 85.1 (C(CH3)3), 44.3 (CH2NHBoc), 28.3 (C(CH3)3). High-resolution mass spectrometry (HRMS, ESI+) showed an m/z of 258.1101 (calculated value: C13H19NO3Na [M+Na]+, 258.1101; measured value: 258.1094). The NMR data are consistent with literature reports.
References
[1] Patent: WO2012/95628, 2012, A1. Location in patent: Page/Page column 18-19
[2] Patent: WO2006/117549, 2006, A1. Location in patent: Page/Page column 148
[3] Patent: WO2005/12280, 2005, A1. Location in patent: Page/Page column 53
[4] Patent: WO2006/12135, 2006, A1. Location in patent: Page/Page column 49-51
[5] Patent: US2006/293379, 2006, A1. Location in patent: Page/Page column 63
