1,2-Dichloroethane → {2-[2-(2-Benzyloxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-piperidin-1-yl]-1-methyl-2-oxo-ethyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

2-(2-Benzyloxy-5-oxo-tetrahydro-furan-3-ylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (100) was dissolved in 20% TFA in CH2Cl2 (25 mL) and stirred at room temperature for 50 min. The solvent was evaporated and the residual acid azeotroped with CH2Cl (4×). The resulting oil was dissolved in CH2Cl2 (20 mL) and DMF (5 mL), cooled to 0° C. and treated with DIEA (4.7 mL, 27.0 mmol), Boc-alanine (970 mg, 5.1 mmol), HOBT (924 mg, 6.8 mmol) and EDC (1.31 g, 6.8 mmol) and the solution stirred under N2 for 18 hours. The solvent was concentrated in vacuo then dissolved in EtOAc and washed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine. The organic layer was dried over anhydrous Na2SO4 and evaporated to give an orange solid that was dissolved in CH2Cl2 and added dropwise to diethyl ether to afford a white precipitate. The title compound as a white solid (1.21 g, 73% yield). 1H-NMR (500 MHz, CDCl3) δ 1.10-1.79 (m, 18H), 1.98-2.19 (m, 0.5H), 2.28-2.88 (m, 3H), 2.89-3.13 (m, 0.5H), 3.78-3.95 (m, 0.5H), 4.21-5.16 (m, 5.5H), 5.38-5.59 (m, 0.3H), 5.66 (d, 0.4H), 5.80 (d, 0.3H), 7.24-7.40 (m, 5H). LC-MS (ES+) m/e=490.3 (MH+).

Provenance & Evidence