2-(4'-FLUOROPHENOXY)ETHANOL

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

实验步骤: To 200 ml of 1 M diborane in tetrahydrofuran was added dropwise 17.0 L g of 4-fluorophenoxyacetic acid in 100 ml of tetrahydrofuran at 5°-10° C. The reaction was stirred at room temperature overnight and poured into a mixture of 100 ml of ice and 750 ml of chloroform. The water phase was extracted twice more with 250 ml each of chloroform and the combined organic phase dried. This solution was concentrated to a light yellow oil. This material was placed on the Kugelrohr (vacuum distillation) giving 14.8 g on distillation. The water phase was extracted twice more with 250 ml each of chloroform the combined organic phase dried This solution was concentrated to a light yellow oil This material was placed on the Kugelrohr (vacuum distillation) giving 14.8 g on distillation

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

实验步骤: Diethyl azodicarboxylate (1.25 g, 7.20 mmol) was added to a solution of 2-(4-fluorophenoxy)ethanol (1.12 g, 7.20 mmol), isoindoline-1,3-dione (1.06 g, 7.20 mmol) and triphenylphosphine (1.89 g, 7.20 mmol) in tetrahydrofuran (20 ml) at 0° C. The reaction mixture was stirred at room temperature for 17 hours and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/petroleum ether: 10/90 to 12.5/87.5) to give 2-(2-(4-fluorophenoxy)ethyl)isoindoline-1,3-dione (1.05 g, 51%) as a white solid: LCMS: 286 [M+1]+. concentrated in vacuo The residue was purified by column chromatography (ethyl acetate/petroleum ether: 10/90 to 12.5/87.5)

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

实验步骤: LiAlH4 (378 mg, 10.0 mmol) was added at −15° C. to a solution of tert-butyl 2-(4-fluorophenoxy)acetate (2.03 g, 9.00 mmol) in tetrahydrofuran (10 ml) and stirred at room temperature for 20 minutes. Aqueous 15% NaOH solution (2 ml), Na2SO4 (2.84 g) and H2O (6 ml) were added to the reaction mixture and stirred for 1 hour. The resulting precipitation was filtered off and washed with tetrahydrofuran (30 ml×3). The filtrate was dried over Na2SO4, filtered and concentrated in vacuo to give 2-(4-fluorophenoxy)ethanol (1.12 g, 80%) as yellow oil: LC-MS: 157 [M+1]+. stirred for 1 hour The resulting precipitation was filtered off washed with tetrahydrofuran (30 ml×3) The filtrate was dried over Na2SO4 filtered concentrated in vacuo

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

实验步骤: The title compound was prepared according to the experimentals described for Example 14 above from 2-methanesulfonyl-5,7-diethyl-[1,2,4]triazolo[1,5-a]pyrimidine and 2-(4-fluorophenoxy)ethan-1-ol in 70% yield. EM (calc.): 330.1; MS (ESI) m/e: 331.3 (M+H)+.

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

实验步骤: As for Example 56, 12.5 g of 2-(p-fluorophenoxy) ethanol is reacted with 7 ml of methanesulfonyl chloride in 100 ml of dichloromethane in the presence of 23 ml of triethylamine. The product (18 g) is obtained as a colorless liquid.

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

实验步骤: To 200 ml of 1 Molar diborane in tetrahydrofuran (chilled to 5°-10° C.) is added dropwise 17.0 g of 2-(p-fluorophenoxy)acetic acid in 100 ml of tetrahydrofuran. The mixture is stirred overnight and poured into 100 g of ice and 250 ml of chloroform. The organic layer is separated and the aqueous layer extracted with chloroform. The organic layer and extracts are combined, dried (MgSO4) and the solvent removed under vacuum. The residual pale yellow oil is distilled to give the product (14.8 g) as a colorless oil. The organic layer is separated the aqueous layer extracted with chloroform dried (MgSO4) the solvent removed under vacuum The residual pale yellow oil is distilled

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl 2-(4-fluorophenoxy)acetate (3.12 g, 15.74 mmol) was dissolved in diethyl ether (50 ml) and cooled to about 0° C. Lithium aluminum hydride (1.792 g, 47.2 mmol) was added in portions while maintaining reaction temperature below 35° C. The reaction was allowed to stir at room temperature for one hour. The crude reaction was diluted with ether (50 mL) then cooled in an ice bath and quenched by dropwise addition of water (6.1 mL), then 2 M NaOH (12.2 mL), then water (6.1 mL). The mixture was filtered and concentrated. The crude product was purified on silica gel (4:1 heptane:EtOAc as eluant) to give 2-(4-fluoro-phenoxy)-ethanol (1.36 g, 55%). while maintaining reaction temperature below 35° C The crude reaction then cooled in an ice bath quenched by dropwise addition of water (6.1 mL) The mixture was filtered concentrated The crude product was purified on silica gel (4:1 heptane:EtOAc as eluant)