Trimethylsilylacetylene → HCID 69794947, compound

HRID 2181684Notes

Reaction equation

HRID 2181684 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][C:15]3[O:19][CH:18]=[C:17](Br)[C:16]=3[CH:21]=1)=[O:11])[CH2:2]2.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[CH3:35][Si:36]([C:39]#[CH:40])([CH3:38])[CH3:37]>O1CCOCC1.CCOC(C)=O.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[CH:13]=[CH:14][C:15]3[O:19][CH:18]=[C:17]([C:40]#[C:39][Si:36]([CH3:38])([CH3:37])[CH3:35])[C:16]=3[CH:21]=1)=[O:11])[CH2:2]2

Participants

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 9975089HCID 9975089, compound

Product 1

HCID 69794947HCID 69794947, compoundYield 73.1%

Reagents, catalysts & solvents 3

HCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

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)+.

Workup

  1. washis washed with 1:1:0.1 NaCl/water/conc
  2. dry with materialNH4OH (4×25 ml), and the organic layer is dried (K2CO3)
  3. customThe volatiles are removed in vacuo
  4. customthe residue is chromatographed over 30 g silica gel (230-400 mesh)
  5. washeluting with 7% MeOH/CHCl3+1% conc. NH4OH
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f0374c139c3f4a95b1e1730a55a4b1d9
Source dataset
uspto-grants-2005_05
Patent number
US06894042B2

Reaction notes

Loading…