Triphenylphosphine → HCID 86685699, compound

HRID 536576Notes

Reaction equation

HRID 536576 reaction equation
[CH3:1][O:2][C:3](=[O:27])[CH2:4][CH2:5][C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([CH2:12][C:13]2[CH:18]=[C:17](Br)[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[N:7]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:47][Si:48]([C:51]#[CH:52])([CH3:50])[CH3:49]>CN(C=O)C.[Cu]I>[CH3:1][O:2][C:3](=[O:27])[CH2:4][CH2:5][C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([CH2:12][C:13]2[CH:18]=[C:17]([C:52]#[C:51][Si:48]([CH3:50])([CH3:49])[CH3:47])[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[N:7]=1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 86685698HCID 86685698, compound

Product 1

HCID 86685699HCID 86685699, compoundYield 48.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-{1-[5-Bromo-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-propionic acid methyl ester (0.0774 g, 0.18 mmol), [PdCl2(PPh3)]2 (0.007 g, 0.01 mmol), PPh3 (0.0094 g, 0.018 mmol) mmol), CuI (2 mg, 0.01 mmol), trimethylsilylacetylene (0.0196 g, 0.2 mmol), Et2N (0.07314 g, 2.72 mmol in DMF (1 ml) heated at 120° C. in a microwave reactor under a N2 atmosphere for 50 min. The mixture was partitioned between 0.1M HCl and EtOAc. The organic layer was washed with brine, dried (MgSO4) and evaporated to dryness. The residue was purified by MPLC (20 g SiO2 cartridge, eluent 90% iso-hexane-10% EtOAc) yielding 3-{1-[5-trimethylsilanylethynyl-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-propionic acid methyl ester (0.0396 g). This was dissolved in THF (20 ml), MeOH (20 ml), glacial acetic acid (8 ml) and Bu4NF solution (24 ml, 1M) was added. The mixture was stirred at RT overnight then heated at 60° C. for 3 hours, thereafter cooled to RT and partitioned between sat. NH4Cl solution and EtOAc, the organic layer was washed with brine, dried (MgSO4) and evaporated to dryness. The residue was purified by MPLC (20 g SiO2 cartridge, eluent 85% iso-hexane-15% EtOAc) yielding 3-{1-[5-Ethynyl-2-(2-ethyl-butoxy)-benzyl]-5-methyl-1H-pyrazol-3-yl}-propionic acid methyl ester (0.0078 g) which was converted to the title compound following the method in Example 1, Step 8.

Workup

  1. customThe mixture was partitioned between 0.1M HCl and EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. customevaporated to dryness
  5. customThe residue was purified by MPLC (20 g SiO2 cartridge, eluent 90% iso-hexane-10% EtOAc)

Sources & evidence

ORD record
ord-60b2600711c240b2a81f94a85b8123bc
Source dataset
uspto-grants-2014_10
Patent number
US08859606B2

Reaction notes

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