Hydrochloric Acid → HCID 131730439, compound

Participants

Reaction Conditions

Reaction Steps

Trans-methyl 2-cyclohexyl-4-(3-ethoxy-3-oxopropanoyl)piperidine-1-carboxylate (349 mg, 1.03 mmol) (from example 79, step 1) was dissolved in MeOH (5 mL) and cooled to −40° C. Sodium hydroxide (41.1 mg, 1.03 mmol) dissolved in water (0.500 mL) was added dropwise and the colourless solution continued to stir at −40° C. for 30 min. Hydroxylamine (50% by weight in water, 0.063 mL, 1.03 mmol) was added dropwise. The resulting solution was stirred at −40° C. for 2 h 20 min. The mixture was then rapidly poured into a prewarmed (80° C.) solution of 6 M hydrogen chloride (5 mL, 30.00 mmol) and the mixture continued to stir at 80° C. for 20 min. The solvent was evaporated and MTBE/water added. The phases were separated and the organic phase was dried over Na2SO4 and evaporated to yield a yellow oil. The compound was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 15-75% Acetonitrile in H2O/MeCN/AcOH 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. Trans-methyl 2-cyclohexyl-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (170 mg, 53%) was isolated. 1H NMR (400 MHz, cdcl3) δ 0.82-1.08 (m, 2H), 1.08-1.32 (m, 3H), 1.45-1.83 (m, 8H), 1.89-2.02 (m, 1H), 2.12-2.23 (m, 1H), 2.79-3.04 (m, 2H), 3.70 (s, 3H), 3.87-4.83 (m, 2H), 5.64 (s, 1H). MS m/z 309 (M+H)+

Provenance & Evidence