苯氧基锂 溶液

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (80 mg, 0.35 mmol), and lithium phenoxide (1 mL, 1.04 mmol, 1M solution in THF) were suspended in DMAC (2 mL), and stirred for 4 h at 100° C. The reaction mixture was cooled to room temperature, and diluted with H2O. The resulting precipitate was filtered, washed with H2O, and dried under vacuum to provide 137 (22 mg, 22% yield) as a tan solid. LC-MS (M+H=289, obsd.=289). 1H NMR (400 MHz, d6-DMSO): δ 12.12 (s, 1H), 9.08 (d, 1H), 8.42 (dd, 1H), 8.28 (d, 1H), 7.88 (td, 1H), 7.70 (t, 1H), 7.55 (m, 2H), 7.35 (m, 3H), 6.55 (d, 1H). The reaction mixture was cooled to room temperature The resulting precipitate was filtered washed with H2O dried under vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-(Trifluoromethyl)phenol 5 (10.82 g, 66.85 mmol) in THF (30 mL) was added lithium-tert-butoxide (5.34 g, 66.85 mmol) at 0° C. and stirred at RT for 30 min. The resulting lithium phenoxide solution was added drop wise to a solution of (2S)-1-oxo-1-(pyrrolidin-1-yl)propan-2-yl 2-bromo-2-(4-chlorophenyl)acetate 4 (25.0 g, 66.85 mmol) in THF (160 ml) at −5° C. The reaction mixture was stirred for 4 h at −5° C. To the solution was added a pre-mixed solution of H2O2 (30% solution, 151 g, 1336.989 mmol) and LiOH,H2O (6.8 g, 167.11 mmol) in water (150 mL) at 0-5° C. over 30 min. The reaction mixture was stirred 0-5° C. for 1 h and quenched with saturated aqueous sodium bisulfite (200 ml). The reaction mixture was made acidic (pH ˜2) with 1(N) HCl at cooling condition. The organic layer was separated and concentrated under reduced pressure. The crude residue was dissolved in ethyl acetate (150 mL) and washed with water (2×80 mL) followed by brine solution (80 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash chromatography on 100-200 mesh silica-gel (12-15% ethyl acetate-hexane) to afford (2R)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetic acid 7 (11.2 g, 51%) as off white solid. The reaction mixture was stirred for 4 h at −5° C The reaction mixture was stirred 0-5° C. for 1 h quenched with saturated aqueous sodium bisulfite (200 ml) at cooling condition The organic layer was separated concentrated under reduced pressure The crude residue was dissolved in ethyl acetate (150 mL) washed with water (2×80 mL) The organic layer was dried over Na2SO4 concentrated under reduced pressure The crude residue was purified by flash chromatography on 100-200 mesh silica-gel (12-15% ethyl acetate-hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-(Trifluoromethyl)phenol 5 (10.82 g, 66.85 mmol) in THF (30 mL) was added lithium-tert-butoxide (5.34 g, 66.85 mmol) at 0° C. and stirred at RT for 30 min. The resulting lithium phenoxide solution was added drop wise to a solution of (2S)-1-oxo-1-(pyrrolidin-1-yl)propan-2-yl 2-bromo-2-(4-chlorophenyl)acetate 4 (25.0 g, 66.85 mmol) in THF (160 ml) at −5° C. The reaction mixture was stirred for 4 h at −5° C. To the solution was added a pre-mixed solution of H2O2 (30% solution, 151 g, 1336.989 mmol) and LiOH,H2O (6.8 g, 167.11 mmol) in water (150 mL) at 0-5° C. over 30 min. The reaction mixture was stirred 0-5° C. for 1 h and quenched with saturated aqueous sodium bisulfite (200 ml). The reaction mixture was made acidic (pH ˜2) with 1(N) HCl at cooling condition. The organic layer was separated and concentrated under reduced pressure. The crude residue was dissolved in ethyl acetate (150 mL) and washed with water (2×80 mL) followed by brine solution (80 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash chromatography on 100-200 mesh silica-gel (12-15% ethyl acetate-hexane) to afford (2R)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetic acid 7 (11.2 g, 51%) as off white solid. The reaction mixture was stirred for 4 h at −5° C The reaction mixture was stirred 0-5° C. for 1 h quenched with saturated aqueous sodium bisulfite (200 ml) at cooling condition The organic layer was separated concentrated under reduced pressure The crude residue was dissolved in ethyl acetate (150 mL) washed with water (2×80 mL) The organic layer was dried over Na2SO4 concentrated under reduced pressure The crude residue was purified by flash chromatography on 100-200 mesh silica-gel (12-15% ethyl acetate-hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (−)-i-Propyl allyloxybenzene (Evans, P. A.; Leahy, D. K. J. Am. Chem. Soc. 2000, 122, 5012): The general procedure was followed with lithium phenoxide (200 mg, 2.0 mmol) and 2-hexenyl methylcarbonate (160 mg, 1.0 mmol) in THF (2 mL). The reaction was conducted at 50° C. for 14 h. 1H NMR analysis of the mixture indicated the ratio of regioisomers to be 92/8. The residue was purified by flash chromatography on silica gel (0-1% Et2O/Hexanes) to afford 162 mg of the title compound as an oil. [93%, Rf 0.90 (5% Et2O/Hexanes)]. 1H NMR (500 MHz, CDCl3) δ 7.23 (m, 2H), 6.91 (m, 3H), 5.84 (ddd, J=17.3, 10.6, 6.2 Hz, 1H), 5.25 (d, J=17.4 Hz, 1H), 5.20 (d, J=10.6 Hz, 1H), 4.59 (dt, J=6.8, 6.0 Hz, 1H), 1.83-1.74 (m, 1H), 1.68-1.61 (m, 1H), 1.58-1.38 (m, 2H), 0.96 (t, J=7.4 Hz, 3H); 13C NMR (125.77 MHz, CDCl3) δ 158.4, 138.2, 129.3, 120.6, 116.2, 116.0, 78.6, 37.7, 18.6, 14.0. HPLC analysis indicated an enantiomeric excess of 92% [Chiralcel® OD-H column, eluting with 99.9:0.1 hexane/i-PrOH, 0.6 mL/min, 220 nm; major enantiomer tR, 13.3, minor enantiomer tR 15.8 min]. The residue was purified by flash chromatography on silica gel (0-1% Et2O/Hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (−)-i-Propyl allyloxybenzene (Evans, P. A.; Leahy, D. K. J. Am. Chem. Soc. 2000, 122, 5012): The general procedure was followed with lithium phenoxide (200 mg, 2.0 mmol) and 2-hexenyl methylcarbonate (160 mg, 1.0 mmol) in THF (2 mL). The reaction was conducted at 50° C. for 14 h. 1H NMR analysis of the mixture indicated the ratio of regioisomers to be 92/8. The residue was purified by flash chromatography on silica gel (0-1% Et2O/Hexanes) to afford 162 mg of the title compound as an oil. [93%, Rf 0.90 (5% Et2O/Hexanes)]. 1H NMR (500 MHz, CDCl3) δ 7.23 (m, 2H), 6.91 (m, 3H), 5.84 (ddd, J=17.3, 10.6, 6.2 Hz, 1H), 5.25 (d, J=17.4 Hz, 1H), 5.20 (d, J=10.6 Hz, 1H), 4.59 (dt, J=6.8, 6.0 Hz, 1H), 1.83-1.74 (m, 1H), 1.68-1.61 (m, 1H), 1.58-1.38 (m, 2H), 0.96 (t, J=7.4 Hz, 3H); 13C NMR (125.77 MHz, CDCl3) δ 158.4, 138.2, 129.3, 120.6, 116.2, 116.0, 78.6, 37.7, 18.6, 14.0. HPLC analysis indicated an enantiomeric excess of 92% [Chiralcel® OD-H column, eluting with 99.9:0.1 hexane/i-PrOH, 0.6 mL/min, 220 nm; major enantiomer tR, 13.3, minor enantiomer tR 15.8 min]. The residue was purified by flash chromatography on silica gel (0-1% Et2O/Hexanes)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 1-Chloro-5H-benzo[c][1,8]naphthyridin-6-one (80 mg, 0.35 mmol), and lithium phenoxide (1 mL, 1.04 mmol, 1M solution in THF) were suspended in DMAC (2 mL), and stirred for 4 h at 100° C. The reaction mixture was cooled to room temperature, and diluted with H2O. The resulting precipitate was filtered, washed with H2O, and dried under vacuum to provide 137 (22 mg, 22% yield) as a tan solid. LC-MS (M+H=289, obsd.=289). 1H NMR (400 MHz, d6-DMSO): δ 12.12 (s, 1H), 9.08 (d, 1H), 8.42 (dd, 1H), 8.28 (d, 1H), 7.88 (td, 1H), 7.70 (t, 1H), 7.55 (m, 2H), 7.35 (m, 3H), 6.55 (d, 1H). The reaction mixture was cooled to room temperature The resulting precipitate was filtered washed with H2O dried under vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-(Trifluoromethyl)phenol 5 (10.82 g, 66.85 mmol) in THF (30 mL) was added lithium-tert-butoxide (5.34 g, 66.85 mmol) at 0° C. and stirred at RT for 30 min. The resulting lithium phenoxide solution was added drop wise to a solution of (2S)-1-oxo-1-(pyrrolidin-1-yl)propan-2-yl 2-bromo-2-(4-chlorophenyl)acetate 4 (25.0 g, 66.85 mmol) in THF (160 ml) at −5° C. The reaction mixture was stirred for 4 h at −5° C. To the solution was added a pre-mixed solution of H2O2 (30% solution, 151 g, 1336.989 mmol) and LiOH,H2O (6.8 g, 167.11 mmol) in water (150 mL) at 0-5° C. over 30 min. The reaction mixture was stirred 0-5° C. for 1 h and quenched with saturated aqueous sodium bisulfite (200 ml). The reaction mixture was made acidic (pH ˜2) with 1(N) HCl at cooling condition. The organic layer was separated and concentrated under reduced pressure. The crude residue was dissolved in ethyl acetate (150 mL) and washed with water (2×80 mL) followed by brine solution (80 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by flash chromatography on 100-200 mesh silica-gel (12-15% ethyl acetate-hexane) to afford (2R)-2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetic acid 7 (11.2 g, 51%) as off white solid. The reaction mixture was stirred for 4 h at −5° C The reaction mixture was stirred 0-5° C. for 1 h quenched with saturated aqueous sodium bisulfite (200 ml) at cooling condition The organic layer was separated concentrated under reduced pressure The crude residue was dissolved in ethyl acetate (150 mL) washed with water (2×80 mL) The organic layer was dried over Na2SO4 concentrated under reduced pressure The crude residue was purified by flash chromatography on 100-200 mesh silica-gel (12-15% ethyl acetate-hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (−)-i-Propyl allyloxybenzene (Evans, P. A.; Leahy, D. K. J. Am. Chem. Soc. 2000, 122, 5012): The general procedure was followed with lithium phenoxide (200 mg, 2.0 mmol) and 2-hexenyl methylcarbonate (160 mg, 1.0 mmol) in THF (2 mL). The reaction was conducted at 50° C. for 14 h. 1H NMR analysis of the mixture indicated the ratio of regioisomers to be 92/8. The residue was purified by flash chromatography on silica gel (0-1% Et2O/Hexanes) to afford 162 mg of the title compound as an oil. [93%, Rf 0.90 (5% Et2O/Hexanes)]. 1H NMR (500 MHz, CDCl3) δ 7.23 (m, 2H), 6.91 (m, 3H), 5.84 (ddd, J=17.3, 10.6, 6.2 Hz, 1H), 5.25 (d, J=17.4 Hz, 1H), 5.20 (d, J=10.6 Hz, 1H), 4.59 (dt, J=6.8, 6.0 Hz, 1H), 1.83-1.74 (m, 1H), 1.68-1.61 (m, 1H), 1.58-1.38 (m, 2H), 0.96 (t, J=7.4 Hz, 3H); 13C NMR (125.77 MHz, CDCl3) δ 158.4, 138.2, 129.3, 120.6, 116.2, 116.0, 78.6, 37.7, 18.6, 14.0. HPLC analysis indicated an enantiomeric excess of 92% [Chiralcel® OD-H column, eluting with 99.9:0.1 hexane/i-PrOH, 0.6 mL/min, 220 nm; major enantiomer tR, 13.3, minor enantiomer tR 15.8 min]. The residue was purified by flash chromatography on silica gel (0-1% Et2O/Hexanes)