Synthesis
GENERAL STEPS: Example 8-1; To a 100 mL Schlenk tube purged with nitrogen was added 4.00 g (30.5 mmol) of (S)-tert-leucine and 40 mL of tetrahydrofuran, and the temperature of the reaction system was adjusted to 10°C. Over 5 min, 1.46 g (61.0 mmol) of lithium borohydride was added to the suspension in batches, followed by adjusting the temperature of the system to 20 °C. Over 30 minutes, 7.44 g (67.1 mmol) of trimethylmethylsilyl chloride was added slowly and dropwise, then the mixture was heated to 65 °C and stirred continuously at this temperature for 3 hours. Upon completion of the reaction, the mixture was cooled to 10 °C and quenched by the slow dropwise addition of 4 mL of methanol over 20 min. After concentrating the reaction mixture using a rotary evaporator, 40 mL of 4 M aqueous sodium hydroxide solution was added and stirred for 1 hour at room temperature. Subsequently, 40 mL of tert-butyl methyl ether was added for extraction and the organic layer was separated and dried with anhydrous sodium sulfate. After filtration to remove the desiccant, the tert-butyl methyl ether was removed by atmospheric pressure distillation. Finally, the 70 to 75 °C fraction was collected by reduced pressure distillation (0.3 kPa) to give 2.96 g of (S)-tert-leucinol in 83% yield.
References
[1] Journal of the American Chemical Society, 2003, vol. 125, # 21, p. 6362 - 6363
[2] Chemical Communications, 2010, vol. 46, # 3, p. 445 - 447
[3] Beilstein Journal of Organic Chemistry, 2013, vol. 9, p. 1637 - 1642
[4] Journal of Organic Chemistry, 1992, vol. 57, # 17, p. 4732 - 4740
[5] Organic Letters, 2018, vol. 20, # 16, p. 4806 - 4810