Ethyl bromoacetate → (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate

To a suspension of NaH (7.44 g, 161 mmol) in anhydrous DMF (50 mL) at 0-5° C. was added dropwise a solution of (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (17.45 g, 54 mmol) in anhydrous DMF (100 mL), the reaction mixture was stirred for 1 hr at rt. A solution of ethyl bromoacetate (17.82 g, 11.87 mL, 107 mmol) in anhydrous DMF (100 mL) was added dropwise to the above mixture at 0-5° C. After addition, the reaction mixture was stirred for 2-3 hr at rt. The reaction mixture was poured into saturated aqueous NH4Cl and EtOAc (1000 mL) was added. The organic layer was washed with water (3×200 mL) and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified on silica gel chromatography to afford (R)-tert-butyl 3-((R)-(3-chlorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate (14 g, 64% yield).

1. additionAfter addition
2. stirringthe reaction mixture was stirred for 2-3 hr at rt
3. additionwas added
4. washThe organic layer was washed with water (3×200 mL) and brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified on silica gel chromatography

ORD 기록

ord-0d247517581e452e90f18f502e5d92e4

출처 데이터셋

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08198453B2