1-benzyl-2,2-dimethylpiperidin-4-ol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine 1-benzyl-2,2-dimethyl-piperidin-4-ol (preparation 9) 1.08 g, 4.92 mmol), N,N-dimethylformamide (20 mL) and 95% sodium hydride (0.12 g, 4.92 mmol) and stir. After 30 min., add 2,6-dichloropyridine (0.67 g, 4.52 mmol), stir and heat at 120° C. After 18 hr., cool to ambient temperature and partition between water (100 mL) and ethyl acetate (100 mL). Separate the organic layer and wash the aqueous layer with ethyl acetate (2×100 mL). Combine the organic layers, wash with water (5×100 mL), wash with aqueous NaCl solution, dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 9:1 hexane:ethyl acetate to obtain of the title compound (0.57 g, 38%). Mass spectrum (electrospray): m/z=331.1 (M+1); 1H NMR (CDCl3): 7.5 (dd, 1H), 7.3 (m, 5H), 6.8 (d, 1H), 6.6 (d, 1H), 5.2 (m, 1H), 3.9 (d, 1H), 3.2 (d, 1H), 2.65 (m, 1H), 2.4 (m, 1H), 2.0 (m, 2H), 1.7 (m, 1H), 1.6 (m, 1H), 1.3 (s, 3H), 1.2 (s, 3H). After 18 hr , cool to ambient temperature partition between water (100 mL) and ethyl acetate (100 mL) Separate the organic layer wash the aqueous layer with ethyl acetate (2×100 mL) Combine the organic layers, wash with water (5×100 mL) wash with aqueous NaCl solution dry over sodium sulfate filter concentrate Purify the residue by silica gel flash chromatography eluting with 9:1 hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Combine 1-benzyl-2,2-dimethyl-piperidin-4-one (1.0 g, 4.6 mmol) and tetrahydrofuran (20 mL) and cool to 0° C. Add lithium aluminum hydride (0.175 g, 4.6 mmol) with stirring. After 30 min., warm to ambient temperature. After 30 min., quench the reaction mixture with water (50 mL). Extract with ethyl acetate (2×75 mL), combine the organic layers and wash with aqueous NaCl solution (50 mL), dry over sodium sulfate, filter and concentrate to obtain the title compound (1.0 g, 100%). Mass spectrum (electrospray): m/z=220.1 (M+1); 1H NMR (CDCl3): 7.3 (m, 5H), 4.0 (m, 1H), 3.8 (m, 1H), 3.0 (m, 1H), 2.6 (m, 1H), 2.3 (m, 1H), 1.8 (m, 2H), 1.4 (m, 3H), 1.25 (s, 3), 1.1 (s, 3H). After 30 min. quench the reaction mixture with water (50 mL) Extract with ethyl acetate (2×75 mL) wash with aqueous NaCl solution (50 mL) dry over sodium sulfate filter concentrate