Acetonitrile → 1'-(2,3-Dichloropyridin-4-yl)spiro[1-benzofuran-3,4'-piperidine]

反応式

[Cl:1][C:2]1[C:7]([Cl:8])=[C:6](I)[CH:5]=[CH:4][N:3]=1.CC[N:12]([CH:16]([CH3:18])C)[CH:13]([CH3:15])C.[C:19]([O-:22])(O)=O.[Na+].[CH3:24][C:25]#N>>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([N:12]2[CH2:13][CH2:15][C:7]3([C:6]4[CH:5]=[CH:4][CH:25]=[CH:24][C:19]=4[O:22][CH2:2]3)[CH2:18][CH2:16]2)[CH:5]=[CH:4][N:3]=1

参加物

反応物 4

HCID 6342Acetonitrile

HCID 81531Diisopropylethylamine

HCID 516892Sodium Bicarbonate

HCID 448870382,3-Dichloro-4-iodopyridine

生成物 1

HCID 866679871'-(2,3-Dichloropyridin-4-yl)spiro[1-benzofuran-3,4'-piperidine]

反応条件

温度: 110 °C

実験手順

A mixture of intermediate D10 (3 g, 10.953 mmol), 4-spiro-[3-(2,3-dihydro-benzofuran)]piperidine [CAS 171-77-7] (2.28 g, 12.049 mmol and DIPEA (7.63 ml, 43.814 mmol) in CH3CN (100 ml) was heated in a sealed tube at 110° C. for 3 days. The mixture was then treated with NaHCO3 (aqueous sat. solution) and extracted with EtOAc. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 4% as eluent), the desired fractions were collected and concentrated in vacuo to yield intermediate D48 (2.9 g, 63%) as a white solid. M.P. 177.2° C.