(2S)-1-chloro-3-(2,4,5-trifluorophenyl)propan-2-ol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S)-3-(2,4,5-trifluorophenyl)-1-chloro-2-propanol obtained in step 1 was dissolved in 50 ml of methanol, and NaOH (2.3 g) was added dropwise thereto. A mixture was stirred for 1 hour, and methanol was removed therefrom under a reduced pressure. Water (50 ml) and ethyl acetate (50 ml) were added thereto, and the organic layer formed thereafter was separated. The separated organic layer was washed with satuated saline, dried over MgSO4, and filtered to remove MgSO4. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound (7.6 g; yield: 85%). methanol was removed Water (50 ml) and ethyl acetate (50 ml) were added the organic layer formed thereafter was separated The separated organic layer was washed with satuated saline dried over MgSO4 filtered to remove MgSO4 The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2N i-PrMgCl (26 ml) suspended in THF was added dripwise to the 2,4,5-trifluorobenzene bromide (9.55 g) dissolved in THF (30 ml) at −15° C. for 60 min. CuI (0.72 g) was added thereto at −15° C., and heated to −10° C. (S)-epichlorohydrin (4.1 ml) dissolved in THF (40 ml) was added slowly to the resulting mixture, and stirred at 0° C. for 1 hour. Satuated NH4Cl (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture, and the organic layer formed thereafter was separated. The separated organic layer was washed with 50 ml of satuated saline, dried over MgSO4, and filtered to remove MgSO4. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound. was added slowly to the resulting mixture the organic layer formed thereafter was separated The separated organic layer was washed with 50 ml of satuated saline dried over MgSO4 filtered to remove MgSO4 The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S)-3-(2,4,5-trifluorophenyl)-1-chloro-2-propanol obtained in step 1 was dissolved in 50 ml of methanol, and NaOH (2.3 g) was added dropwise thereto. A mixture was stirred for 1 hour, and methanol was removed therefrom under a reduced pressure. Water (50 ml) and ethyl acetate (50 ml) were added thereto, and the organic layer formed thereafter was separated. The separated organic layer was washed with satuated saline, dried over MgSO4, and filtered to remove MgSO4. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound (7.6 g; yield: 85%). methanol was removed Water (50 ml) and ethyl acetate (50 ml) were added the organic layer formed thereafter was separated The separated organic layer was washed with satuated saline dried over MgSO4 filtered to remove MgSO4 The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S)-3-(2,4,5-trifluorophenyl)-1-chloro-2-propanol obtained in step 1 was dissolved in methanol (50 ml), and NaOH (2.3 g) was added dropwise thereto. The resulting mixture was stirred for 1 hour and methanol was removed therefrom under a reduced pressure. Water (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture, and the organic layer formed thereafter was separated. The separated organic layer was washed with satuated saline, dried over MgSO4, and filtered to remove MgSO4. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound (6.8 g; yield: 80%). methanol was removed Water (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture the organic layer formed thereafter was separated The separated organic layer was washed with satuated saline dried over MgSO4 filtered to remove MgSO4 The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (Mg) (1.26 g) was suspended in tetrahydrofuran (THF) (10 ml), and a drop of 1,2-dibromoethane was added thereto. To the resulting mixture, 2,4,5-trifluorobenzene bromide (0.55 g) was added dropwise slowly and then stirred for 30 min. 2,4,5-trifluorobenzene bromide (9.0 g) dissolved in THF (50 ml) was added slowly dropwise to the resulting mixture for 30 min and then stirred at room temperature for 1 hour. CuI (0.72 g) was added to the resulting mixture and the reaction temperature was cooled to 0° C. (S)-epichlorohydrin (4.1 ml) dissolved in THF (40 ml) was added dropwise to the resulting mixture slowly over 30 min, heated to room temperature, and stirred for 2 hours. Satuated NH4Cl (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture, and the organic layer formed thereafter was separated. The separated organic layer was washed with 50 ml of satuated saline, dried over MgSO4, and filtered. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound. was added slowly dropwise to the resulting mixture for 30 min stirred at room temperature for 1 hour was added dropwise to the resulting mixture slowly over 30 min stirred for 2 hours the organic layer formed thereafter was separated The separated organic layer was washed with 50 ml of satuated saline dried over MgSO4 filtered The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (Mg) (1.26 g) was suspended in tetrahydrofuran (THF) (10 ml), and a drop of 1,2-dibromoethane was added thereto. To the resulting mixture, 2,4,5-trifluorobenzene bromide (0.55 g) was added dropwise slowly and then stirred for 30 min. 2,4,5-trifluorobenzene bromide (9.0 g) dissolved in THF (50 ml) was added slowly dropwise to the resulting mixture for 30 min and then stirred at room temperature for 1 hour. CuI (0.72 g) was added to the resulting mixture and the reaction temperature was cooled to 0° C. (S)-epichlorohydrin (4.1 ml) dissolved in THF (40 ml) was added dropwise to the resulting mixture slowly over 30 min, heated to room temperature, and stirred for 2 hours. Satuated NH4Cl (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture, and the organic layer formed thereafter was separated. The separated organic layer was washed with 50 ml of satuated saline, dried over MgSO4, and filtered. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound. was added slowly dropwise to the resulting mixture for 30 min stirred at room temperature for 1 hour was added dropwise to the resulting mixture slowly over 30 min stirred for 2 hours the organic layer formed thereafter was separated The separated organic layer was washed with 50 ml of satuated saline dried over MgSO4 filtered The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 84.4 g of 1-bromo-2,4,5-trifluorobenzene and 42.1 mL of tetrahydrofuran were added to 250 mL flask, and the resulting reaction solution was cooled to −15-20° C. Under nitrogen atmosphere, 20 mL of isopropylmagnesium chloride [2.0 M tetrahydrofuran solution] was dropped to the reaction solution, and stirred at 0-5° C. for 2 hours to produce Grinard reagent. 31.6 mL of (S)-epichlorohydrin and 42.1 mL of tetrahydrofuran were added to another 250 mL flask; the resulting reaction solution was cooled to −15-−20° C.; and then 7.6 g of copper iodide was added thereto. 42.1 mL of the Grinard reagent produced under nitrogen atmosphere was dropped, and stirred for 3 hours while the reaction temperature was maintained at −15-−20° C. 297 mL of 2 N hydrochloric acid aqueous solution that was cooled at 0-5° C. was dropped to the reaction solution, and then extracted with 297 mL of isopropylether. An organic layer was dehydrated with sodium sulfate, and then concentrated under reduced pressure to obtain 89.8 g of a title compound. the resulting reaction solution to produce Grinard reagent the resulting reaction solution was cooled to −15-−20° C. 42.1 mL of the Grinard reagent produced under nitrogen atmosphere was dropped stirred for 3 hours while the reaction temperature was maintained at −15-−20° C was dropped to the reaction solution extracted with 297 mL of isopropylether concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S)-3-(2,4,5-trifluorophenyl)-1-chloro-2-propanol obtained in step 1 was dissolved in 50 ml of methanol, and NaOH (2.3 g) was added dropwise thereto. A mixture was stirred for 1 hour, and methanol was removed therefrom under a reduced pressure. Water (50 ml) and ethyl acetate (50 ml) were added thereto, and the organic layer formed thereafter was separated. The separated organic layer was washed with satuated saline, dried over MgSO4, and filtered to remove MgSO4. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound (7.6 g; yield: 85%). methanol was removed Water (50 ml) and ethyl acetate (50 ml) were added the organic layer formed thereafter was separated The separated organic layer was washed with satuated saline dried over MgSO4 filtered to remove MgSO4 The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2N i-PrMgCl (26 ml) suspended in THF was added dripwise to the 2,4,5-trifluorobenzene bromide (9.55 g) dissolved in THF (30 ml) at −15° C. for 60 min. CuI (0.72 g) was added thereto at −15° C., and heated to −10° C. (S)-epichlorohydrin (4.1 ml) dissolved in THF (40 ml) was added slowly to the resulting mixture, and stirred at 0° C. for 1 hour. Satuated NH4Cl (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture, and the organic layer formed thereafter was separated. The separated organic layer was washed with 50 ml of satuated saline, dried over MgSO4, and filtered to remove MgSO4. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound. was added slowly to the resulting mixture the organic layer formed thereafter was separated The separated organic layer was washed with 50 ml of satuated saline dried over MgSO4 filtered to remove MgSO4 The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2S)-3-(2,4,5-trifluorophenyl)-1-chloro-2-propanol obtained in step 1 was dissolved in methanol (50 ml), and NaOH (2.3 g) was added dropwise thereto. The resulting mixture was stirred for 1 hour and methanol was removed therefrom under a reduced pressure. Water (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture, and the organic layer formed thereafter was separated. The separated organic layer was washed with satuated saline, dried over MgSO4, and filtered to remove MgSO4. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound (6.8 g; yield: 80%). methanol was removed Water (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture the organic layer formed thereafter was separated The separated organic layer was washed with satuated saline dried over MgSO4 filtered to remove MgSO4 The organic solvent was removed from the filtrate under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium (Mg) (1.26 g) was suspended in tetrahydrofuran (THF) (10 ml), and a drop of 1,2-dibromoethane was added thereto. To the resulting mixture, 2,4,5-trifluorobenzene bromide (0.55 g) was added dropwise slowly and then stirred for 30 min. 2,4,5-trifluorobenzene bromide (9.0 g) dissolved in THF (50 ml) was added slowly dropwise to the resulting mixture for 30 min and then stirred at room temperature for 1 hour. CuI (0.72 g) was added to the resulting mixture and the reaction temperature was cooled to 0° C. (S)-epichlorohydrin (4.1 ml) dissolved in THF (40 ml) was added dropwise to the resulting mixture slowly over 30 min, heated to room temperature, and stirred for 2 hours. Satuated NH4Cl (50 ml) and ethyl acetate (50 ml) were added to the resulting mixture, and the organic layer formed thereafter was separated. The separated organic layer was washed with 50 ml of satuated saline, dried over MgSO4, and filtered. The organic solvent was removed from the filtrate under a reduced pressure to obtain the title compound. was added slowly dropwise to the resulting mixture for 30 min stirred at room temperature for 1 hour was added dropwise to the resulting mixture slowly over 30 min stirred for 2 hours the organic layer formed thereafter was separated The separated organic layer was washed with 50 ml of satuated saline dried over MgSO4 filtered The organic solvent was removed from the filtrate under a reduced pressure