Potassium Carbonate → Methyl 5-chloro-2-ethynylbenzoate

A suspension of potassium carbonate (5.0 g, 36 mmol) in methanol (20 ml) was stirred under nitrogen whilst adding a solution of methyl 5-chloro-2-[2-(trimethylsilyl)ethynyl]benzoate (4.8 g, 18.0 mmol) in methanol (50 ml). The resulting mixture was stirred at 20° C. for 2 hours. The reaction mixture was filtered, and the solid washed with methanol. The filtrate was concentrated in-vacuo and then re-dissolved in methanol (50 ml) and carefully treated with acetyl chloride (4.0 ml). The reaction mixture was stirred overnight and concentrated in-vacuo. TBME (50 ml) was added to the residue and the resulting suspension filtered. The filtrate was washed with a saturated solution of NaHCO3 (40 ml). The layers were separated and the aqueous phase was extracted with TBME (3×40 ml). The combined organics were dried over MgSO4, filtered and concentrated in-vacuo. The crude residue was purified by flash column chromatography (50 g Isolute cartridge, 0-10% TBME:Heptanes) to give the title compound (1.2 g, 33%) as a white solid. LC-MS 93%, m/z=194.9, 196.9; 1H NMR (500 MHz, Chloroform-d) δ ppm 7.94 (s, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.46 (d, J=8.4 Hz, 1H), 3.95 (s, 3H), 3.44 (s, 1H).

1. stirringThe resulting mixture was stirred at 20° C. for 2 hours
2. filtrationThe reaction mixture was filtered
3. washthe solid washed with methanol
4. concentrationThe filtrate was concentrated in-vacuo
5. dissolutionre-dissolved in methanol (50 ml)
6. additioncarefully treated with acetyl chloride (4.0 ml)
7. stirringThe reaction mixture was stirred overnight
8. concentrationconcentrated in-vacuo
9. additionTBME (50 ml) was added to the residue
10. filtrationthe resulting suspension filtered
11. washThe filtrate was washed with a saturated solution of NaHCO3 (40 ml)
12. customThe layers were separated
13. extractionthe aqueous phase was extracted with TBME (3×40 ml)
14. dry with materialThe combined organics were dried over MgSO4
15. filtrationfiltered
16. concentrationconcentrated in-vacuo
17. customThe crude residue was purified by flash column chromatography (50 g Isolute cartridge, 0-10% TBME:Heptanes)

ORD record

ord-2e88de1c93d3407ebe8f96923de60b28

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376422B2