1 -(4-Chlorophenyl)-1 -phenylethanol

Uses

1-(4-Chlorophenyl)-1-phenylethanol (Clemastine EP Impurity C) is used in the synthetic preparation of rhodium-catalyzed arylation of nitriles, ketones and imines with tetrafluoroborate or arylboronic acids

Synthesis

1. A solution was prepared by dissolving bromobenzene (20.31 g, 129.35 mmol) in anhydrous tetrahydrofuran (50 mL) under nitrogen protection. 2. The above solution was added slowly and dropwise to a reaction flask containing magnesium shavings (3.88 g, 159.61 mmol), dry tetrahydrofuran (50 mL) and iodine crystals. 3. After heating and refluxing for about 2 hours, the resulting solution of Grignard reagent was cooled to about 0°C. 4. A tetrahydrofuran solution (100 mL) of 1-(4-chlorophenyl)ethanone (10.0 g, 64.69 mmol) was slowly added dropwise to the cooled Grignard reagent solution described above at 0°C. 5. After the dropwise addition was completed, the reaction mixture was stirred at room temperature for about 18 hours. 6. Upon completion of the reaction, the mixture was cooled to about 0°C and the reaction was quenched by slow addition of saturated ammonium chloride solution. 7. The organic phase was collected after standard extraction using ethyl acetate. 8. The crude product was purified by silica gel column chromatography with petroleum ether solution of 5% ethyl acetate as eluent to afford the title compound 1-(4-chlorophenyl)-1-phenylethanol as an oil (3.80 g, 25% yield). 9. The product was characterized as follows: 1H NMR (400 MHz, CDCl3) δ 1.94 (s, 3H), 2.17 (s, 1H, exchangeable with D2O), 7.23-7.42 (m, 9H). IR (membrane) υ 3414, 3061, 2978, 2927, 2859, 1597, 1489, 1449, 1394 cm-1; MS 215, 217 [(s, 1H, exchangeable with D2O)]. MS 215, 217 [(M+1)-H2O, (M+3)-H2O].

References

[1] Patent: US2009/203763, 2009, A1. Location in patent: Page/Page column 35