Uses
3-(Trifluoromethyl)benzenepropanol-d4 is an intermediate in the synthesis of Cinacalcet-d4 Hydrochloride (C441803), a labeled analogue of Cinacalcet Hydrochloride (C441800), the (R) enantiomer of Cinacalcet which is used in clinical trial in secondary hyperparathyroidism.
Synthesis
To a solution of 14.5 g (72.5 mmol) of purified 3-(3-trifluoromethylphenyl)propargyl alcohol in 50 mL of 2-propanol was added 0.38 g of 10% Pd/C (Selcat Q6). The reaction mixture was subjected to hydrogenation at a temperature of 42-45°C and a pressure of 5 bar until all feedstocks were completely converted (about 5 hours). Upon completion of the reaction, it was filtered to remove the catalyst and the catalyst was washed with a small amount of 2-propanol. Subsequently, the filtrate was concentrated by evaporation under reduced pressure. The crude product obtained (14.5 g, 100.0%) was purified by distillation under reduced pressure, resulting in 10.5 g (yield: 72.1%) of the target product 3-(3-trifluoromethylphenyl)propanol as an almost colorless oil (boiling point: 58-60 °C/1.1-1.5 mbar).
References
[1] Organic Letters, 2019, vol. 21, # 1, p. 65 - 69
[2] Patent: US2010/267988, 2010, A1. Location in patent: Page/Page column 4
[3] Patent: EP2327684, 2011, A1. Location in patent: Page/Page column 6
[4] Patent: US2011/124917, 2011, A1. Location in patent: Page/Page column 3
