反应详情

A solution of 3,4-dichlorophenylacetic acid (4.45 g) and 1,1'-carbonyldiimidazole (4.16 g) in dry tetrahydrofuran (60 ml) was stirred at room temperature for 20 min before adding a solution of the product of stage (i) (4.0 g, 60:40 mixture of trans:cis isomers) in dry tetrahydrofuran. This solution was stirred for 16 h under nitrogen and concentrated in vacuo. Column chromatography of the residue on UGI alumina (10 cm diameter, 20 cm length) with graded elution from dichloromethane to dichloromethane:methanol (9:1) removed polar material. The mixture obtained was converted to the hydrochloride salt and crystallised from ethyl acetate:methanol (1:2). The mother liquors were concentrated and the residue was crystallised from the same solvent. The mother liquors from this second recrystallisation gave the title compound upon concentration as an amorphous solid (2.8 g), m.p. 115°-120°, which contained a 93:7 mixture of trans:cis isomers by h.p.l.c.

1. concentrationconcentrated in vacuo
2. washColumn chromatography of the residue on UGI alumina (10 cm diameter, 20 cm length) with graded elution from dichloromethane to dichloromethane:methanol (9:1)
3. customremoved polar material
4. customThe mixture obtained
5. customcrystallised from ethyl acetate:methanol (1:2)
6. concentrationThe mother liquors were concentrated
7. customthe residue was crystallised from the same solvent
8. customThe mother liquors from this second recrystallisation