Hydrochloric Acid → HCID 68503570, compound

Participants

Reaction Steps

A solution of cis-methyl 2-benzyl-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (2.15 g, 6.18 mmol) (from Example 1, Step 1) in MeOH (0.75 mL) was added to a solution of NaOH (0.26 g, 6.55 mmol) in MeOH/H2O (5 mL/0.3 mL) at −30° C. After 10 minutes was added a solution of hydroxylamine hydrochloride (0.86 g, 12.4 mmol) and NaOH (0.49 g, 12.4 mmol) in MeOH (6.1 mL) and H2O (6.1 mL). Stirring was continued at −30° C. for 30 minutes. The reaction mixture was then poured into concentrated HCl (7 mL) held at 80° C. The solution was stirred for 30 minutes. The organic solvent was evaporated and the aqueous phase extracted with ether (×3). The combined organic phases were dried over Na2SO4, and evaporated to yield a solid, 2.2 g. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 20-70% acetonitrile in H2O/MeCN/FA 95/5/0.2 buffer, over 18 minutes with a flow of 19 mL/minutes. The title compound was isolated (1.1 g, 57%). 1H NMR (600 MHz, cdcl3) δ 1.76-2.15 (m, 4H), 2.63 (m, 1H), 2.82 (m, 1H), 2.87-3.03 (m, 1H), 3.03-3.22 (m, 1H), 3.61 (s, 3H), 3.99 (m, 1H), 4.19-4.33 (m, 1H), 5.71 (s, 1H), 7.01-7.37 (m, 5H). MS m/z 317 (M+H)+.

Provenance & Evidence