4-tert-butylpiperidine Hydrochloride → Piperidine, 4-(1,1-dimethylethyl)-

Dissolve 4-tert-butylpiperidine hydrochloride (5.0 g, 28.1 mmol) in 150 mL of sodium bicarbonate (saturated aqueous solution), then extract three times with DCM. Combine the organic fractions; dry over sodium sulfate; filter; collect the filtrate; and concentrate under reduced pressure to give 4-tert-butylpiperidine free base. Add N-[(1S)-2,2,2-trifluoro-1-(4-formylphenyl)-ethyl]-methanesulfonamide (7.0 g, 24.9 mmol) to the free base and dissolve the mixture in DCM (150 mL). Stir the mixture at ambient temperature for two hours, and then add sodium triacetoxyborohydride (26.37 g, 124.44 mmol) and acetic acid (1.71 mL, 29.87 mmol). Stir for 72 hours at ambient temperature. Quench the reaction with the addition of 50% saturated sodium bicarbonate solution. Separate the layers, and extract the aqueous layer twice with EtOAc. Combine the organic layers; dry over sodium sulphate; filter; collect the filtrate; and concentrate under reduced pressure. Purify the crude material with silica gel flash column chromatography eluting with MeOH in DCM (0-7%). Collect and concentrate the appropriate fractions under reduced pressure to give the desired compound as a free base (ee>98%). Dissolve the free base in a mixture of MeOH and DCM (1:1, 30 mL). Add HCl (1.0 M in diethyl ether, 40 mL) and swirl the mixture for one minute. Concentrate under reduced pressure to afford the title compound (8.2 g, 74.4%). MS (m/z): 407 (M-HCl+1).

1. extractionextract three times with DCM
2. dry with materialdry over sodium sulfate
3. filtrationfilter
4. customcollect the filtrate
5. concentrationand concentrate under reduced pressure

ORD record

ord-f7c70134a79e4144871383c92db0f802

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073856B2