Water → (R)-1-(2-Methyl-pyridin-4-yl)-3-o-tolyl-3-(4-trimethylsilanylethynyl-phenyl)-propan-1-one

HRID 1617816Notes

Reaction equation

HRID 1617816 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1.[C:26]([Si:28]([CH3:31])([CH3:30])[CH3:29])#[CH:27].O.COC(C)(C)C>N1CCCCC1>[CH3:18][C:14]1[CH:13]=[C:12]([C:10](=[O:11])[CH2:9][C@@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[C:5]2[CH:6]=[CH:7][C:2]([C:27]#[C:26][Si:28]([CH3:31])([CH3:30])[CH3:29])=[CH:3][CH:4]=2)[CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 4

HCID 962WaterHCID 15413tert-Butyl methyl etherHCID 66111TrimethylsilylacetyleneHCID 66666695(R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

Product 1

HCID 67015635(R)-1-(2-Methyl-pyridin-4-yl)-3-o-tolyl-3-(4-trimethylsilanylethynyl-phenyl)-propan-1-oneYield 61%

Reagents, catalysts & solvents 1

HCID 8082PiperidineSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (R)-3-(4-bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one (example 142, step 2, 150 mg) in piperidine (3 mL) were added under argon copper(I) iodide (3.6 mg) and tetrakis-triphenylphosphine palladium(0) (22 mg). The reaction mixture was heated at 50° C. and ethynyltrimethylsilane (480 μL) was added. The reaction mixture was stirred at 50° C. overnight. water and tert-butyl methyl ether were added, the phases were separated and the inorganic one was extracted with tert-butyl methyl ether (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (15% to 50% ethyl acetate in n-heptane) to yield the title compound as a light yellow oil (105 mg, 61%), MS (ESI+): m/z=412.4 ([M+H]+).

Workup

  1. customthe phases were separated
  2. extractionthe inorganic one was extracted with tert-butyl methyl ether (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel (15% to 50% ethyl acetate in n-heptane)

Sources & evidence

ORD record
ord-5c28b3fd283346ceb6918a632bc05304
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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