Synthesis
General procedure for the synthesis of tert-butyl (3-hydroxymethyl-benzyl)-carboxylate from 3-(N-Boc-aminomethyl)benzoic acid: Boc-Mamb-OH (1.765 g, 7.02 mmol) was dissolved in 20 mL of anhydrous THF and cooled in an ice-water bath to 0°C. Subsequently, N-methylmorpholine (0.77 mL, 7.0 mmol) and isobutyl chloroformate (0.91 mL, 7.0 mmol). The reaction mixture was stirred in an ice bath for 10 min before being filtered through a medium porosity glass filter and the precipitate was washed with 2 × 10 mL of anhydrous THF. The filtrate was re-placed in an ice-water bath and cooled, and sodium borohydride (0.815 g, 21.5 mmol) was added, followed by the slow addition of 10 mL of methanol. The reaction was continued for 30 min and then the mixture was concentrated to dryness. The residue was resuspended in 80 mL of ethyl acetate and washed sequentially with 2 x 40 mL of aqueous 1 M sodium bisulfate, 2 x 40 mL of saturated aqueous sodium bicarbonate and 40 mL of brine. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to dryness to afford the target compound tert-butyl (3-hydroxymethyl-benzyl)-carboxylate (1.542 g, 6.51 mmol, 93% yield).ESI(+)MS m/z: 260 [M+Na]+.
References
[1] Patent: WO2008/5457, 2008, A2. Location in patent: Page/Page column 56
[2] Patent: WO2011/21209, 2011, A1. Location in patent: Page/Page column 69; 72
[3] Patent: US2012/101099, 2012, A1. Location in patent: Page/Page column 28; 30
[4] Journal of Medicinal Chemistry, 2018, vol. 61, # 3, p. 946 - 979
[5] Patent: WO2004/89892, 2004, A2. Location in patent: Page 106
