반응 #2268866

반응 방정식

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-3-bromo-1-benzofuran-5-carboxamide

tri(t-butyl)phosphine

trimethylsilylacetylene

→

N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-3-[(trimethylsilyl)ethynyl]-1-benzofuran-5-carboxamide

수율 73.1%

용매

EtOAc

dioxane

반응 조건

후처리

1. 1
   세척is washed with 1:1:0.1 NaCl/water/conc
2. 2
   건조NH4OH (4×25 ml), and the organic layer is dried (K2CO3)
3. 3
   기타The volatiles are removed in vacuo
4. 4
   기타the residue is chromatographed over 30 g silica gel (230-400 mesh)
5. 5
   세척eluting with 7% MeOH/CHCl3+1% conc. NH4OH
6. 6
   농축concentrated

실험 절차

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-3-bromo-1-benzofuran-5-carboxamide (350 mg, 1.0 mmol) is combined with bis(benzonitrile)palladium dichloride (57 mg, 0.15 mmol), cuprous iodide (19 mg, 0.10 mmol), tri(t-butyl)phosphine (658 μL, 0.325 mmol), trimethylsilylacetylene (170 μL, 1.2 mmol), and DIA (168 μL, 1.2 mmol) in dioxane (3 ml) in a dry flask under nitrogen. The reaction is stirred overnight at RT, is diluted with EtOAc (25 ml), is washed with 1:1:0.1 NaCl/water/conc. NH4OH (4×25 ml), and the organic layer is dried (K2CO3). The volatiles are removed in vacuo and the residue is chromatographed over 30 g silica gel (230-400 mesh) eluting with 7% MeOH/CHCl3+1% conc. NH4OH. The appropriate fractions are combined and concentrated to afford 268 mg (73%) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-3-[(trimethylsilyl)ethynyl]-1-benzofuran-5-carboxamide as a pale foam. HRMS (ESI) calcd for C21H26N2O2SI+H: 367.1841, found 367.1852 (M+H)+.

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