Synthesis
GENERAL STEPS: To an anhydrous triethylamine (TEA) solution of 4-bromobenzyl alcohol (935 mg, 5 mmol) was sequentially added dichlorobis(triphenylphosphine)palladium(II) (Pd(PPh3)2Cl2, 175 mg, 0.25 mmol), cuprous iodide (CuI, 48 mg, 0.25 mmol) and tri-tert-butylphosphine (P(t-Bu)3, 51 mg. 0.25 mmol) and stirred for 5 min under nitrogen (N2) protection. Subsequently, trimethylsilylacetylene (980 mg, 10 mmol) was added slowly and dropwise. The reaction mixture was placed in a microwave reactor and heated at 130 °C for 4 hours. After completion of the reaction, it was cooled to room temperature and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the residue was extracted three times with ethyl acetate (EtOAc) and water (H2O). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate (Na2SO4), and then purified by silica gel column chromatography (petroleum ether/ethyl acetate, 4:1) to afford 4-(trimethylsilylethynyl)benzylmethanol (670 mg, 66%) as a brown oil.
To a solution of 4-(trimethylsilylethynyl)benzylmethanol (250 mg, 1.23 mmol) in tetrahydrofuran (THF) was added tetrabutylammonium fluoride (TBAF, 500 mg, 2.45 mmol) in batches. The reaction mixture was stirred at 0 °C, gradually warmed to room temperature and continued stirring for 3 hours. After completion of the reaction, the solvent was removed under reduced pressure and the residue was extracted three times with ethyl acetate (EtOAc) and water (H2O). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate (Na2SO4), and then purified by silica gel column chromatography (petroleum ether/ethyl acetate, 4:1) to afford 4-ethynylbenzylmethanol (170 mg, 100%) as a brown oil.1H NMR (400 MHz, CDCl3) δ 7.45-7.49 (m, 2H), 7.21- 7.26 (m, 2H), 4.69 (s, 1H), 4.65 (s, 2H).
References
[1] Chemistry - A European Journal, 2017, vol. 23, # 50, p. 12190 - 12197
[2] Synthesis (Germany), 2014, vol. 46, # 3, p. 348 - 356
[3] Angewandte Chemie - International Edition, 2004, vol. 43, # 29, p. 3814 - 3818
[4] Patent: WO2018/14802, 2018, A1. Location in patent: Paragraph 0364
[5] Chemistry - A European Journal, 2013, vol. 19, # 29, p. 9452 - 9456
