Triethylamine → 2-(6-trimethylsilanylethynyl-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71770Notes

Reaction equation

HRID 71770 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:17][C:16]2[CH:18]=[C:19](Br)[CH:20]=[CH:21][C:15]=2[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:23]([Si:25]([CH3:28])([CH3:27])[CH3:26])#[CH:24].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:17][C:16]2[CH:18]=[C:19]([C:24]#[C:23][Si:25]([CH3:28])([CH3:27])[CH3:26])[CH:20]=[CH:21][C:15]=2[N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 581852752-(6-bromo-1H-benzimidazol-2-yl)pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666201682-(6-trimethylsilanylethynyl-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 62.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(6-bromo-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (309 mg, 0.84 mmol), ethynyl-trimethyl-silane (1.2 mL, 8.4 mmol), tetrakis(triphenylphosphine)palladium (97 mg, 0.08 mmol), copper(I) iodide (32 mg, 0.16 mmol) and triethylamine (0.7 mL, 5.04 mmol) in 5 ml DMF was heated to 80° C. for 8 hours. The reaction mixture was cooled and dissolved in ethyl acetate and washed with 5% lithium chloride aqueous solution. The organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane) to give 2-(6-trimethylsilanylethynyl-1H-benzoimidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, yield 62%). LCMS-ESI−: calc'd for C21H29N3O2Si: 383.56. Found: 384.1 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. washwashed with 5% lithium chloride aqueous solution
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 20 to 100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-78bed1f5ea304d5dadf4fc0169a37a5a
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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