3-Trimethylsilyl-2-propyn-1-ol

Chemical Properties

clear yellow liquid

Uses

Trimethylsilylpropargyl alcohol is used as a reagent to synthesize Isbogrel, a Thromboxane A 2 (TXA 2) synthase inhibitor and also a TXA 2 receptor antagonist that has potential to treat asthma.

Application

3-Trimethylsilyl-2-propyn-1-ol is a colourless transparent liquid which is sensitive to light, air and moisture, and can be used as raw material for organic synthesis or reaction reagent. Alkyllithiums undergo trans addition to 3-(trimethylsilyl)-2-propyn-1-ols to yield (1-lithiovinyl)silanes. Due to unidentified side-reactions, yields do not exceed 20%.

Synthesis

Compound 5 (0.250 g, 1.17 mmol) was added dropwise to a flask containing methanol (4.0 mL) and Amberlyst-15 (0.025 g) under nitrogen protection at a reaction temperature of 0 °C. The reaction mixture was warmed to 40 °C and stirred for 8 hours. Upon completion of the reaction, the resin was removed by filtration and washed with ethyl acetate (10 mL). To the filtrate, 10% aqueous hydrochloric acid (10 mL) was added, followed by extraction of the organic layer with ethyl acetate (3 x 10 mL). The organic phases were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by column chromatography (eluent: hexane/ethyl acetate = 9:1) to afford compound 6 in 96% yield (0.143 g, 1.12 mmol).

References

[1] Tetrahedron, 1996, vol. 52, # 21, p. 7487 - 7510
[2] Journal of the Brazilian Chemical Society, 2013, vol. 24, # 12, p. 1933 - 1941
[3] Chemistry - A European Journal, 2015, vol. 21, # 27, p. 9662 - 9665
[4] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1987, p. 1077 - 1082
[5] Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4650 - 4652