Ethyl bromoacetate → HCID 59201428, Verbindung

To a suspension of NaH (3.5 g, 88.4 mmol) in THF (100 mL) at 0-5° C. was added dropwise a solution of (R)-tert-butyl 3-((2,3-difluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (9.6 g, 29.5 mmol) in THF (50 mL), the reaction mixture was stirred for 1 h at rt. A solution of ethyl bromoacetate (14.7 g, 88.4 mmol) in THF (50 mL) was added dropwise to the above mixture, and then refluxed for 3-5 h. The reaction mixture was poured into saturated aqueous NH4Cl, then extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified on silica gel chromatography to afford (3R)-tert-butyl 3-((2,3-difluorophenyl)(2-ethoxy-2-oxoethoxy)methyl)piperidine-1-carboxylate (9.5 g, 79%). 1H NMR (CDCl3, 400 MHz) δ 7.22 (m, 1H), 7.08 (m, 2H), 4.62 (d, 2H), 4.33 (d, 2H), 4.18 (q, 3H), 3.95 (m, 4H), 3.82 (d, 2H), 2.77 (m, 4H), 1.88 (m, 3H), 1.44 (s, 9H), 1.26 (t, 3H).

1. temperaturerefluxed for 3-5 h
2. extractionextracted with ethyl acetate
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified on silica gel chromatography

ORD-Eintrag

ord-5a1dbbc88ac34dfbbca4ea20914d2a32

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08487108B2