Ethyl (3S)-piperidine-3-carboxylate → (3S)-ethyl 1-(2-(3-(3,4-diethoxyphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)-2-hydroxyethyl)piperidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

To 3-(3,4-diethoxyphenyl)-7-(oxiran-2-yl)-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 81A, 0.08 g, 0.212 mmol) in a mixture of 2-propanol (1 mL) and dioxane (1.000 mL) was added DMAP (5.18 mg, 0.042 mmol) followed by (S)-ethyl piperidine-3-carboxylate (0.033 mL, 0.212 mmol) at room temperature. The reaction mixture was heated at 60° C. (oil bath temp.) for 26 h, concentrated under reduced pressure, and purified by column chromatography using an ISCO setup (12 g, RediSep® silica gel column). The desired fractions were collected and concentrated to yield (0.03 g, 0.056 mmol, 26.5% yield) of the product as a diastereomeric mixture. The individual diastereomers were separated using a CHIRALCE1® OJ-H column under SFC conditions (25% MeOH with 0.1% diethylamine in CO2). Isomer 1 (7.7 mgs), retention time on chiral HPLC, 4.39 min; Isomer 2 (9 mgs), retention time on chiral HPLC, 6.15 min. The absolute stereochemistry at the carbon anchoring the secondary alcohol, of Isomer 1 and Isomer 2 was not determined.

Provenance & Evidence