(R)-2-AMINO-1,2-DIPHENYL-1-PROPANOL

14316-06-4

100-58-3

78603-93-7

Example 5: Synthesis of (R)-2-Amino-1,1-diphenyl-propan-1-ol: A solution of phenylmagnesium bromide (PhMgBr, 0.87 mol, dissolved in 287 mL of tetrahydrofuran (THF)) was cooled to 0°C under inert atmosphere. Subsequently, D-alanine methyl ester hydrochloride ((R)-1-methoxycarbonyl-ethyl-ammonium chloride, 20 g, 140 mmol) was added in batches over 90 min, keeping the reaction temperature between 0-5 °C. After addition, the reaction mixture was continued to be stirred at 0-5 °C for 30 min and then slowly warmed up to room temperature. After the reaction was carried out at room temperature for 4 h, it was cooled to 0 °C again. A 10% w/w aqueous hydrochloric acid solution (100 mL) was slowly added at 0-5 °C for 60 min. After addition, the mixture was warmed up to room temperature. Next, ethyl acetate (300 mL) and water (400 mL) were added for extraction. After separating the organic and aqueous phases, the aqueous phase was extracted once more with ethyl acetate (200 mL). All organic phases were combined and washed sequentially with water (50 mL) and brine (50 mL). The organic phase was concentrated under vacuum to give about 50 g of residue. Hexane (30 mL) was slowly added to the residue over 30 minutes. The mixture was cooled to 0 °C over a period of 3 hours and aged at 0 °C for 1 hour. Finally, the mixture was filtered, isolated and dried to give (R)-2-amino-1,1-diphenyl-propan-1-ol (30.4 g, 80% yield) as a yellow solid. The product was characterized by 1H NMR (400 MHz, CDCl3), δ 7.64 (dd, J = 7.6, 4.0 Hz, 2H), 7.51 (dd, J = 7.6, 1.4 Hz, 2H), 7.37-7.28 (m, 4H), 7.24-7.17 (m, 2H), 4.18 (q, J = 6.3 Hz, 1H), 0.99 ( d, J = 6.3 Hz, 3H).