4-Bromobutyronitrile → (R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate

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To a suspension of NaH (763 mg, 19.1 mmol) and (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (1.55 g, 4.77 mmol) in CH3CN (20 mL) at 0-5° C. was added dropwise a solution of 4-bromobutyronitrile (3.17 g, 21.5 mmol) in CH3CN (5 mL), the reaction mixture was stirred for overnight at rt. The reaction mixture was poured into saturated aqueous NH4Cl, ethyl acetate (50 mL) was added. The organic layer was washed with water (3×20 mL) and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative HPLC to afford (R)-tert-butyl 3-((R)-(3-chlorophenyl)(3-cyanopropoxy)methyl)piperidine-1-carboxylate (0.44 g, 21% yield). 1H NMR (CD3OD, 400 MHz) δ 7.38-7.28 (m, 3H), 7.22 (m, 1H), 4.22 (m, 1H), 4.02 (d, 1H), 3.86 (d, 1H), 3.34 (m, 2H), 2.77 (q, 2H), 2.56 (t, 2H), 1.62 (m, 1H), 1.59 (m, 1H), 1.43 (s, 9H), 1.35-1.25 (m, 3H), 1.12 (d, 1H).

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