Hydrochloric Acid → 1-Chloro-2-(2,4-difluorophenyl)butane-2,3-diol

To a solution of 0.45 g (1.28 mmol) of 1-chloro-2-(2,4-difluorophenyl)-3-(tert-butyldimethylsilyloxy)butan-2-ol ((2S,3R)/(2R,3R)=91/9)) in 5 mL of methanol was added 0.25 mL of concentrated hydrochloric acid at room temperature. After the completion of the dropwise addition, stirring was performed at room temperature for 18 hours. Then, 10 mL of water was added to stop the reaction, and extraction was performed with 20 mL of ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a crude product as a colorless oil. A quantitative analysis was performed by HPLC. Thereby, the title compound was obtained in a yield of 77% ((2S,3R)/(2R,3R))=90/10) (HPLC, column: CAPCELL PAK C18 TYPE MG manufactured by Shiseido Co. Ltd., mobile phase: acetonitrile/20 mM (potassium) phosphate buffer solution (pH=2.5)=3/7, flow rate: 1.0 mL/min, column temperature: 30° C., detector: UV 210 nm, retention time: 26 minutes (2S,3R), 17 minutes (2R,3R). 1H-NMR (400 MHz, CDCl3) (2S,3R) δ: 0.98 (d, 3H, J=6.6 Hz), 2.50 (brs, 1H), 3.21 (s, 1H), 4.11-4.23 (m, 3H), 6.77-6.80 (m, 1H), 6.91-6.93 (m, 1H), 7.69-7.71 (m, 1H); (2R,3R) δ: 1.93 (dd, 3H, J=6.3, 1.2 Hz), 2.25 (d, 1H, J=5.2 Hz), 3.15 (s, 1H), 3.96 (d, J=11.0 Hz), 4.08 (q, 1H, J=6.3 Hz), 4.35 (d, J=11.2 hz), 6.77-6.80 (m, 1H), 6.91-6.93 (m, 1H), 7.69-7.71 (m, 1H)).

1. additionAfter the completion of the dropwise addition
2. customthe reaction, and extraction
3. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
4. concentrationconcentrated under reduced pressure
5. customto obtain a crude product as a colorless oil

ORD record

ord-3bd40e784eed491d9eee734c479dc83c

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582781B2