4-Chlorobenzaldehyde → 1-Benzylpiperidine

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

1. additionare added
2. washwashed with dilute NaOH
3. dry with materialThe organic layer is then dried over sodium sulfate
4. concentrationconcentrated under vacuum
5. customto provide crude material which
6. customwas purified

ORD record

ord-75b45b08237540ce9e72270b1a7476d2

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08765735B2