Trimethylsilylacetylene → Methyl 5-chloro-2-[2-(trimethylsilyl)ethynyl]benzoate

HRID 2208858Notes

Reaction equation

HRID 2208858 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13]([Si:15]([CH3:18])([CH3:17])[CH3:16])#[CH:14]>[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:12][C:9]1[CH:10]=[CH:11][C:2]([C:14]#[C:13][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 280500Methyl 2-Bromo-5-chlorobenzoate

Product 1

HCID 70872518Methyl 5-chloro-2-[2-(trimethylsilyl)ethynyl]benzoateYield 102.9%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 2-bromo-5-chlorobenzoate (14.8 g, 59 mmol) in TEA (124 ml, 890 mmol) was added copper(I) iodide (338 mg, 1:78 mmol) and triphenylphosphine (778 mg, 2.97 mmol) at room temperature under nitrogen. This mixture had nitrogen bubbled through it for 10 minutes before the addition of ethynyl(trimethyl)silane (12.45 ml, 89 mmol) and Pd(OAc)2 (266 mg, 1.19 mmol). The reaction mixture was stirred at 50° C. for 20 hours before being concentrated under reduced pressure. The residue was dissolved in deionized water (50 ml) and EtOAc (50 ml) and filtered through celite. The filter cake was washed with EtOAc (50 ml) before the phases were separated and the aqueous layer was extracted with EtOAc (2×50 ml). The combined organic extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by FCC (10 g silica, Isolute cartridge, gradient of eluents; 99:1 Heptane:EtOAc to 85:15 Heptane:EtOAc) to give 16.2 g (102.4%) of the title compound as an orange oil that solidified upon standing and contained residual heptane. LC-MS 91%, m/z=267.4/268.9, 1H NMR (500 MHz, Chloroform-d) δ ppm 7.89 (d, J=2.2 Hz, 1H), 7.51 (d, J=8.3 Hz, 1H), 7.41 (dd, J=8.3, 2.3 Hz, 1H), 3.92 (s, 3H), 0.27 (s, 9H).

Workup

  1. concentrationbefore being concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in deionized water (50 ml)
  3. filtrationEtOAc (50 ml) and filtered through celite
  4. washThe filter cake was washed with EtOAc (50 ml) before the phases
  5. customwere separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×50 ml)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by FCC (10 g silica, Isolute cartridge, gradient of eluents; 99:1 Heptane:EtOAc to 85:15 Heptane:EtOAc)

Sources & evidence

ORD record
ord-772a3f6b61d14f158b2c72b92a04202e
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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