General procedure: [R-(4-benzylmorpholin-3-yl)]-methanol hydrochloride (1 eq.), aqueous K3PO4 (4.6 eq.) and EtOAc were mixed and stirred until two clarified phases were formed. The EtOAc layer was separated and the aqueous layer was extracted with fresh EtOAc. The EtOAc layers were combined and added to a flask containing 20 wt% Pd(OH)2/C (50% aqueous wet, 0.10 eq. based on input weight). Di-tert-butyl dicarbonate (1.2 eq.) was then added. The mixture was hydrogenated at 15 psi hydrogen pressure for 4 hours. Upon completion of the reaction (monitored by HPLC), the mixture was filtered through diatomaceous earth and the solvent was replaced with cyclohexane. By crystallization from cyclohexane (7-10 v/v), tert-butyl (R)-3-(hydroxymethyl)morpholine-4-carboxylate was obtained as a white solid (82% yield). The product characterization data were as follows: 1H NMR (CDCl3) δ 1.45 (s, 9H), 3.17 (m, 1H), 3.47 (dt, 1H, J = 3.1, 11.4 Hz), 3.56 (dd, 1H, J = 3.5, 11.9 Hz), 3.7-4.0 (m, 6H); 13C NMR (CDCl3) δ 28.21, 40.01, 52.09, 59.59, 65.97, 66.49, 80.23, 155.30; MS: 218 (M + H)+; Calculated Elemental Analysis (C10H19NO4): C, 55.28; H, 8.81; N, 6.44; Measured Values: C, 55.45; H, 8.87; N, 6.34; Pd <5 ppm HPLC retention time: 5.28 min (YMC Pack ODS-A, 3 μm, 4.6×50 mm column, 10 min gradient, 2.5 mL/min); 100% ee [Chiral HPLC retention time: 13.6 min (Chiralcel OD-RH, 5 μm, 4.6×150 mm column, 20 min isocratic, 1 mL/ min)]. min)].
