2-(2,5-difluorophenyl)ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate (20 mg, 0.043 mmol), 2-(2,5-difluorophenyl)ethanol (33.7 mg, 0.213 mmol) and Ph3P-resin (55.8 mg, 0.213 mmol) in THF (2 mL) was added DEAD (0.014 mL, 0.085 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (0.854 mL, 0.854 mmol) in MeOH (1 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(2,5-difluorophenethoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid (3.2 mg, 5.51 μmol, 12.91% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.33-7.27 (m, 1H), 7.27-7.17 (m, 3H), 7.17-7.11 (m, 1H), 7.07-6.98 (m, 4H), 5.87 (s, 1H), 4.32-4.23 (m, 2H), 3.09 (t, J=6.2 Hz, 2H), 2.80 (t, J=11.9 Hz, 1H), 2.43 (s, 3H), 2.05 (s, 3H), 1.98-1.91 (m, 1H), 1.49 (br. s., 1H), 1.29 (br. s., 1H), 1.18 (d, J=11.7 Hz, 1H), 1.13 (s, 9H), 1.05-0.95 (m, 1H), 0.85 (br. s., 3H), 0.60 (br. s., 3H). LCMS (M+H)=581.2. mixture was filtered to remove polymer concentrated Mixture was then cooled purified by prep-HPLC

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate (20 mg, 0.043 mmol), 2-(2,5-difluorophenyl)ethanol (33.7 mg, 0.213 mmol) and Ph3P-resin (55.8 mg, 0.213 mmol) in THF (2 mL) was added DEAD (0.014 mL, 0.085 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (0.854 mL, 0.854 mmol) in MeOH (1 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(2,5-difluorophenethoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid (3.2 mg, 5.51 μmol, 12.91% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.33-7.27 (m, 1H), 7.27-7.17 (m, 3H), 7.17-7.11 (m, 1H), 7.07-6.98 (m, 4H), 5.87 (s, 1H), 4.32-4.23 (m, 2H), 3.09 (t, J=6.2 Hz, 2H), 2.80 (t, J=11.9 Hz, 1H), 2.43 (s, 3H), 2.05 (s, 3H), 1.98-1.91 (m, 1H), 1.49 (br. s., 1H), 1.29 (br. s., 1H), 1.18 (d, J=11.7 Hz, 1H), 1.13 (s, 9H), 1.05-0.95 (m, 1H), 0.85 (br. s., 3H), 0.60 (br. s., 3H). LCMS (M+H)=581.2. mixture was filtered to remove polymer concentrated Mixture was then cooled purified by prep-HPLC

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300.1 mg (0.88 mmol) of 2-(3-hydroxy-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl ester, 208.6 mg (1.32 mmol) of 2-(2,5-difluoro-phenyl)-ethanol and 346 mg (1.32 mmol) of triphenylphosphine were dissolved in 10 ml of THF. The mixture was cooled in an ice bath, and 355.5 mg (1.76 mmol) of DIAD were added. After stirring overnight, the mixture was evaporated to dryness and the residue was purified by preparative RP HPLC (water/ACN gradient). 340 mg of the title compound were obtained. The mixture was cooled in an ice bath the mixture was evaporated to dryness the residue was purified by preparative RP HPLC (water/ACN gradient)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300.1 mg (0.88 mmol) of 2-(3-hydroxy-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl ester, 208.6 mg (1.32 mmol) of 2-(2,5-difluoro-phenyl)-ethanol and 346 mg (1.32 mmol) of triphenylphosphine were dissolved in 10 ml of THF. The mixture was cooled in an ice bath, and 355.5 mg (1.76 mmol) of DIAD were added. After stirring overnight, the mixture was evaporated to dryness and the residue was purified by preparative RP HPLC (water/ACN gradient). 340 mg of the title compound were obtained. The mixture was cooled in an ice bath the mixture was evaporated to dryness the residue was purified by preparative RP HPLC (water/ACN gradient)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300.1 mg (0.88 mmol) of 2-(3-hydroxy-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl ester, 208.6 mg (1.32 mmol) of 2-(2,5-difluoro-phenyl)-ethanol and 346 mg (1.32 mmol) of triphenylphosphine were dissolved in 10 ml of THF. The mixture was cooled in an ice bath, and 355.5 mg (1.76 mmol) of DIAD were added. After stirring overnight, the mixture was evaporated to dryness and the residue was purified by preparative RP HPLC (water/ACN gradient). 340 mg of the title compound were obtained. The mixture was cooled in an ice bath the mixture was evaporated to dryness the residue was purified by preparative RP HPLC (water/ACN gradient)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300.1 mg (0.88 mmol) of 2-(3-hydroxy-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl ester, 208.6 mg (1.32 mmol) of 2-(2,5-difluoro-phenyl)-ethanol and 346 mg (1.32 mmol) of triphenylphosphine were dissolved in 10 ml of THF. The mixture was cooled in an ice bath, and 355.5 mg (1.76 mmol) of DIAD were added. After stirring overnight, the mixture was evaporated to dryness and the residue was purified by preparative RP HPLC (water/ACN gradient). 340 mg of the title compound were obtained. The mixture was cooled in an ice bath the mixture was evaporated to dryness the residue was purified by preparative RP HPLC (water/ACN gradient)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl iodoacetate (340 μg, 12.9 mmol) was added to an ice cold solution of 2-(2,5-difluoro-phenyl)-ethanol (500 mg, 2.4 mmol), silver trifluoromethanesulfonate (685 mg, 2.7 mmol) and 2,6-di-tert-butylpyridin (820 μl, 3.6 mmol) in dichloromethane (5 ml). The reaction mixture was stirred at ambient temperature for 14 h, diluted with dichloromethane and filtered over speedex. Ice water/0.1 N aqueous HCl 1/1 was added to the filtrate and the filtrate was extracted two times with dichloromethane. The combined extracts were washed with aqueous NaHCO3 solution and brine and dried over sodium sulfate. Removal of the solvent under reduced pressure left a colorless oil which was purified by column chromatography (silica gel, isopropyl acetate/heptane) to give [2-(2,5-difluoro-phenyl)-ethoxy]-acetic acid ethyl ester (320 mg, 1.3 mmol; 54%) as colorless oil. MS: m/e=245.0 [M+H+]. filtered over speedex Ice water/0.1 N aqueous HCl 1/1 was added to the filtrate the filtrate was extracted two times with dichloromethane The combined extracts were washed with aqueous NaHCO3 solution and brine dried over sodium sulfate Removal of the solvent under reduced pressure left a colorless oil which was purified by column chromatography (silica gel, isopropyl acetate/heptane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 300.1 mg (0.88 mmol) of 2-(3-hydroxy-4-methoxy-benzoylamino)-indane-2-carboxylic acid methyl ester, 208.6 mg (1.32 mmol) of 2-(2,5-difluoro-phenyl)-ethanol and 346 mg (1.32 mmol) of triphenylphosphine were dissolved in 10 ml of THF. The mixture was cooled in an ice bath, and 355.5 mg (1.76 mmol) of DIAD were added. After stirring overnight, the mixture was evaporated to dryness and the residue was purified by preparative RP HPLC (water/ACN gradient). 340 mg of the title compound were obtained. The mixture was cooled in an ice bath the mixture was evaporated to dryness the residue was purified by preparative RP HPLC (water/ACN gradient)