1. To a solution of ethynyltriisopropylsilane (20 g, 110 mmol) in ether (180 mL) was slowly added 2.69 M n-butyllithium hexane solution (44.8 mL, 121 mmol) dropwise at 0 °C under nitrogen protection. After the dropwise addition was completed, ether (20 mL) was added additionally and stirring was continued at the same temperature for 15 min.
2. The reaction mixture was cooled to -78 °C with a dry ice-acetone bath, then a solution of N,N-dimethylformamide (DMF, 25.6 mL, 329 mmol) in ether (160 mL) was added slowly and dropwise. After stirring at -78°C for 20 minutes, the mixture was transferred to an ice bath and continued to stir for 1 hour.
3. 5% aqueous sulfuric acid solution (240 mL) was added to the reaction mixture and stirred for 10 minutes under ice bath cooling. The organic layer was separated, washed sequentially with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure to give the crude product (22.6 g).
4. The crude product was dissolved in methanol (300 mL), hydroxylamine hydrochloride (11.2 g, 161 mmol) and sodium bicarbonate (13.54 g, 161 mmol) were added, and stirred at room temperature for 20 minutes. The reaction solution was diluted with ethyl acetate and concentrated under reduced pressure. Water and ethyl acetate were added to extract the aqueous layer. The organic layer was washed with saturated brine, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the intermediate (24.36 g).
5. 1 g of the intermediate was dissolved in tetrahydrofuran (20 mL) and allyl bromide (0.576 mL, 6.65 mmol) was added under cooling in an ice bath. Subsequently, aqueous sodium hypochlorite solution (6.6 mL) was added dropwise and stirred for 10 minutes in an ice bath and then for 20 minutes at room temperature. Water and ethyl acetate were added, the organic layer was extracted, washed with saturated brine, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain the crude product (1.18 g).
6. The crude was dissolved in tetrahydrofuran (21 mL), cooled to -78 °C in a dry ice-acetone bath, and tetrahydrofuran solution (3.8 mL, 6.84 mmol) of 1.8 M LDA was added dropwise. After stirring at -78 °C for 15 min, the reaction was quenched by the addition of aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.
7. Finally, purification by silica gel column chromatography (eluent: hexane-ethyl acetate) afforded the target product 3-(triisopropylsilyl)propargyl aldehyde (444 mg, 37% yield).
