反应详情

A solution of 4-[2-(5-bromo-2-chloro-pyridin-4-yl)-acetyl]-piperidine-1-carboxylic acid tert-butyl ester (9.80 g) in tetrahydrofuran (6 mL) is added dropwise to an ice-cold solution of methyl magnesium bromide (1.4 mol/L in toluene/tetrahydrofuran 75:25; 74.0 mL). The reaction mixture is stirred for 30 min before the cooling bath is removed. After stirring the mixture at room temperature for 1 h, the mixture is poured into aqueous NH4Cl solution. The resulting mixture is extracted with ethyl acetate, and the combined extracts are dried (MgSO4) and concentrated. The residue containing significant amounts of starting material is azeotropically dried using toluene and resubmitted to the reaction conditions and work-up procedure described. The crude product is purified by preparative HPLC (column: Waters X-Bridge C18; mobile phase: water+0.125% NH4OH/methanol 90:10→100:0) to give the title compound. Mass spectrum (ESI+): m/z=433/435/437 (Cl+Br) [M+H]+.

1. customis removed
2. stirringAfter stirring the mixture at room temperature for 1 h
3. additionthe mixture is poured into aqueous NH4Cl solution
4. extractionThe resulting mixture is extracted with ethyl acetate
5. dry with materialthe combined extracts are dried (MgSO4)
6. concentrationconcentrated
7. additionThe residue containing significant amounts of starting material
8. customis azeotropically dried
9. customresubmitted to the reaction conditions
10. customThe crude product is purified by preparative HPLC (column: Waters X-Bridge C18; mobile phase: water+0.125% NH4OH/methanol 90:10→100:0)