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

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).

1. additionwas added
2. washThe organic layer was washed with water (3×20 mL) and brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by preparative HPLC

ORDレコード

ord-695bdd89cf9542e49e108f5ae34bf9c9

出典データセット

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08487108B2