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A suspension of tert-butyl 4-(4-chlorophenyl)-4-hydroxy-3-methylpiperidine-1-carboxylate (5.5 g, 16.88 mmol) in concentrated HCl (15 mL, 180 mmol) was stirred until a homogeneous solution was observed. The reaction was then heated to reflux and stirred overnight. The mixture was cooled to 0° C. and treated with the careful, portion-wise addition of solid sodium hydroxide until a pH of ˜13 was achieved. The biphasic mixture was extracted 5× with ethyl acetate, and the combined organic phases were washed with a small amount of brine, dried over sodium sulfate, and concentrated in-vacuo to 3.3 g of a colorless oil. The oil was dissolved in THF (50 mL), and the resulting solution was treated with BOC-anhydride (4.67 mL, 20.13 mmol). The reaction was stirred for two days at room temperature. After this time, the mixture was concentrated in vacuo, and the resulting residue was purified over a 330 g silica gel column, eluting at 100 mL/min with a 0% to 15% ethyl acetate/hexanes gradient followed by 15% ethyl acetate/hexanes to yield the title compound (4.93 g, 16.02 mmol, 88% yield) as a colorless solid. The product isolated contained 15% of tert-butyl 4-(4-chlorophenyl)-5-methyl-5,6-dihydropyridine-1(2H)-carboxylate, resulting from a byproduct in the previous step. The material was used as-is. MS (ESI+)=252.2 (M+tert-Bu)+.

1. temperatureThe reaction was then heated
2. temperatureto reflux
3. stirringstirred overnight
4. additiontreated with the careful,
5. extractionThe biphasic mixture was extracted 5× with ethyl acetate
6. washthe combined organic phases were washed with a small amount of brine
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in-vacuo to 3.3 g of a colorless oil
9. dissolutionThe oil was dissolved in THF (50 mL)
10. stirringThe reaction was stirred for two days at room temperature
11. concentrationAfter this time, the mixture was concentrated in vacuo
12. customthe resulting residue was purified over a 330 g silica gel column
13. washeluting at 100 mL/min with a 0% to 15% ethyl acetate/hexanes gradient