(tert-Butyldimethylsilyloxy)acetaldehyde

Chemical Properties

Clear colorless to straw colored liquid

Uses

Employed in the construction of the key tetrahydropyran subunit in a recent synthesis of the marine natural product (–)-dactylodide.

Synthesis

Oxalyl chloride (13.7 mL, 162.2 mmol) was dissolved in anhydrous dichloromethane (400 mL) under nitrogen protection and cooled to -78°C. Dimethyl sulfoxide (25.1 mL, 353.9 mmol) was added slowly and stirred for 30 minutes. Subsequently, a solution of 2-((tert-butyldimethylsilyl)oxy)ethanol (26.0 g, 147.5 mmol) in anhydrous dichloromethane (100 mL) was added dropwise. After maintaining -78 °C and continuing to stir for 30 min, triethylamine (102.74 mL, 737.0 mmol) was added slowly and dropwise. The reaction mixture was stirred at -78 °C for another 30 min, then gradually warmed up to room temperature and continued stirring for 1 h. The reaction mixture was then stirred at -78 °C for 1 h. The reaction mixture was then gradually warmed up to room temperature. The pH of the reaction mixture was adjusted to 4 with aqueous 2N hydrochloric acid and then extracted with dichloromethane (3 x 400 mL). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-((tert-butyldimethylsilyl)oxy)acetaldehyde (34.0 g, 100%) as a colorless oil. The product can be used directly in the subsequent reaction without further purification.

References

[1] Organic Letters, 2016, vol. 18, # 18, p. 4534 - 4537
[2] Patent: WO2017/24018, 2017, A1. Location in patent: Paragraph 00132
[3] Patent: US2016/122345, 2016, A1. Location in patent: Paragraph 0115; 0118
[4] Patent: US9481674, 2016, B1. Location in patent: Page/Page column 47; 48
[5] Patent: WO2017/87608, 2017, A1. Location in patent: Paragraph 00125; 00128