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

HRID 1616476Notes

Reaction equation

HRID 1616476 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, 889.82 mmol) was added copper(I) iodide (338 mg, 1.78 mmol) and triphenylphosphine (778 mg, 2.97 mmol) at room temperature and 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 methyl 5-chloro-2-[2-(trimethylsilyl)ethynyl]benzoate as an orange oil that solidified upon standing. Sample contained heptane. LC-MS 91%, 2.57 min (3 minute LC-MS method), 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-b4b8b578670a4f0aaa005b42ba106bf8
Source dataset
uspto-grants-2014_07
Patent number
US08765732B2

Reaction notes

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