Ammonium Chloride → 1-Chloro-2-(2,5-difluorophenyl)-3-pivaloyloxybutan-2-ol

Participants

Reaction Conditions

Reaction Steps

A solution of 2,5-difluorophenylmagnesium bromide prepared from 5.79 g (30.0 mmol) of 2,5-difluorobromobenzene and 0.759 g (31.2 mmol) of magnesium by the same method as that in Example 3 was cooled to 0° C., and a solution of 3.10 g (15.0 mmol) of (R)-1-chloro-3-pivaloyloxybutan-2-one in 15 mL of toluene was added dropwise thereto. After the completion of the dropwise addition, stirring was continued for another 1 hour, and 10 mL of a saturated aqueous solution of ammonium chloride was added to stop the reaction. Furthermore, 10 mL of water was added, and extraction was performed with ethyl acetate (20 mL×2). After drying over anhydrous sodium sulfate, concentration was performed under reduced pressure to obtain a crude product. A quantitative analysis was performed by HPLC. Thereby, the title compound was obtained in a yield of 63% ((2S,3R)/(2R,3R)=94/6) (HPLC, column: YMC-A302 manufactured by YMC Co. Ltd., mobile phase: acetonitrile/20 mM (potassium) phosphate buffer solution (pH=2.5)=6/4, flow rate: 1.0 mL/min, column temperature: 30° C., detector: UV 210 nm, retention time: 17.0 minutes (2S,3R), 13 minutes (2R,3R)). 1H-NMR (400 MHz, CDCl3) (2S,3R) δ: 1.07 (d, 3H, J=6.3 Hz), 1.24 (s, 9H), 3.86 (d, 1H, J=11.5 Hz), 4.20 (d, 1H, 11.5 Hz), 5.42 (q, 1H, J=6.3 Hz), 7.00-7.03 (m, 2H), 7.40-7.44 (m, 1H); (2R,3R) δ: 1.03 (s, 9H), 1.58 (d, 3H, J=6.3 Hz), 3.91 (d, 1H, J=11.5 Hz), 4.28 (d, 1H, 11.5 Hz), 5.31 (q, 1H, J=6.3 Hz), 6.99-7.02 (m, 2H), 7.26-7.37 (m, 1H).

Provenance & Evidence