4-Chlorobenzaldehyde → 1-Benzylpiperidine

Participants

Reaction Steps

Racemic 3-bromo-4,5-dihydroisoxazole III-43 was dissolved in trifluoroacetic acid (0.20 M with respect to isoxazole) and stirred at room temperature for 1 h. The solvent is then removed under vacuum and the crude residue is azeotroped with toluene (2×) to provide a the trifluoroacetic acid salt as a white solid which is then is dissolved in methylene chloride (0.06 M with respect to isoxozaole) after which triethylamine (2.5 equiv) and 4-chlorobenzaldehyde (1.25 equiv) are added followed by sodium triacetoxyborohydride (1.5 equiv). The reaction is allowed to stir for 16 h after which point is diluted with ethyl acetate and washed with dilute NaOH and then brine. The organic layer is then dried over sodium sulfate and concentrated under vacuum to provide crude material which was purified using flash silica gel chromatography (ethyl acetate/hexanes) to provide N-benzylpiperidine III-45 as a white solid. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=316.6 m/z. Activity: C

Provenance & Evidence