3-环已基-1-丙醇

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: 3-Cyclohexyl-1-propanol (5.00 g) was dissolved in methylene chloride (50 ml), triphenylphosphine (10.2 g) and N-bromosuccinimide (6.90 g) were added under ice-cooling, and the mixture was stirred under ice-cooling for 1 hr, and further at room temperature for 1 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Diethyl ether (100 ml) was added, and the precipitated triphenylphosphine oxide was filtered off. The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone) to give the object product (7.17 g) as a colorless oil. cooling cooling for 1 hr The reaction mixture was washed with water and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure Diethyl ether (100 ml) was added the precipitated triphenylphosphine oxide was filtered off The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone)

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

实验步骤: Cyclohexylpropyl alcohol (237 mL, 1.56 mol) was added to a suspension of NaH (66.0 g, 1.65 mol) in tetrahydrofuran (1.40 L). A solution of 5-Chloro-1-(4-nitro-phenyl)-1H-tetrazole (320 g, 1.42 mol) in tetrahydrofuran (900 mL) was added dropwise over 1.5 hours. The reaction was allowed to cool to room temperature and stirred overnight. The mixture was concentrated in vacuo to a solid. The solid was dissolved in ethyl acetate, washed with saturated aqueous sodium chloride solution (2×), dried (Na2SO4), and filtered through silica gel (700 g). The red filtrate was concentrated in vacuo until product began to precipitate from solution. Hexane was added and the slurry filtered to provide a tan solid (320 g, 64%). Mp 82-88° C. (dec); 1H NMR (CDCl3, 300 MHz) δ 8.43 (d, 9.2 Hz, 2H), 8.04 (d, 9.2 Hz, 2H), 4.70 (t, 7.0 Hz, 2H), 1.96 (m, 2H), 1.75-1.64 (m, 5H), 1.39-1.13 (m, 6H), 0.97-0.87 (m, 2H); MS (CI) m/z 332 (MH+); Anal. calcd for C16H21N5O3: C, 57.99; H, 6.39; N, 21.13. Found: C, 57.80; H, 6.35; N, 21.02; Rf=0.43 (N). The mixture was concentrated in vacuo to a solid The solid was dissolved in ethyl acetate washed with saturated aqueous sodium chloride solution (2×) dried (Na2SO4) filtered through silica gel (700 g) The red filtrate was concentrated in vacuo until product to precipitate from solution Hexane was added the slurry filtered

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

实验步骤: Cyclohexylpropyl alcohol (237 mL, 1.56 mol) was added to a suspension of NaH (66.0 g, 1.65 mol) in tetrahydrofuran (1.40 L). A solution of 5-Chloro-1-(4-nitro-phenyl)-1H-tetrazole (320 g, 1.42 mol) in tetrahydrofuran (900 mL) was added dropwise over 1.5 hours. The reaction was allowed to cool to room temperature and stirred overnight. The mixture was concentrated in vacuo to a solid. The solid was dissolved in ethyl acetate, washed with saturated aqueous sodium chloride solution (2×), dried (Na2SO4), and filtered through silica gel (700 g). The red filtrate was concentrated in vacuo until product began to precipitate from solution. Hexane was added and the slurry filtered to provide a tan solid (320 g, 64%). Mp 82-88° C. (dec); 1H NMR (CDCl3, 300 MHz) δ 8.43 (d, 9.2 Hz, 2 H), 8.04 (d, 9.2 Hz, 2 H), 4.70 (t, 7.0 Hz, 2 H), 1.96 (m, 2 H), 1.75-1.64 (m, 5 H), 1.39-1.13 (m, 6 H), 0.97-0.87 (m, 2 H); MS (CI) m/z 332 (MH+); Anal. calcd for C16H21N5O3 : C, 57.99; H, 6.39; N, 21.13. Found: C, 57.80; H, 6.35; N, 21.02; Rf =0.43 (N). The mixture was concentrated in vacuo to a solid The solid was dissolved in ethyl acetate washed with saturated aqueous sodium chloride solution (2×) dried (Na2SO4) filtered through silica gel (700 g) The red filtrate was concentrated in vacuo until product to precipitate from solution Hexane was added the slurry filtered

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

实验步骤: Cyclohexylpropyl alcohol (237 mL, 1.56 mol) was added to a suspension of NaH (66.0 g, 1.65 mol) in tetrahydrofuran (1.40 L). A solution of 5-Chloro-1-(4-nitro-phenyl)-1H-tetrazole (320 g, 1.42 mol) in tetrahydrofuran (900 mL) was added dropwise over 1.5 hours. The reaction was allowed to cool to room temperature and stirred overnight. The mixture was concentrated in vacuo to a solid. The solid was dissolved in ethyl acetate, washed with saturated aqueous sodium chloride solution (2×), dried (Na2SO4), and filtered through silica gel (700 g). The red filtrate was concentrated in vacuo until product began to precipitate from solution. Hexane was added and the slurry filtered to provide a tan solid (320 g, 64%). Mp 82-88° C. (dec); 1H NMR (CDCl3, 300 MHz) δ 8.43 (d, 9.2 Hz, 2 H), 8.04 (d, 9.2 Hz, 2 H), 4.70 (t, 7.0 Hz, 2 H), 1.96 (m, 2 H), 1.75-1.64 (m, 5 H), 1.39-1.13 (m, 6 H), 0.97-0.87 (m, 2 H); MS (CI) m/z 332 (MH+); Anal. calcd for C16H21N5O3 : C, 57.99; H, 6.39; N, 21.13. Found: C, 57.80; H, 6.35; N, 21.02; Rf =0.43 (N). The mixture was concentrated in vacuo to a solid The solid was dissolved in ethyl acetate washed with saturated aqueous sodium chloride solution (2×) dried (Na2SO4) filtered through silica gel (700 g) The red filtrate was concentrated in vacuo until product to precipitate from solution Hexane was added the slurry filtered

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

实验步骤: Ethyl 4-(4-hydroxy-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (285 mg, 0.898 mmol) was weighed into a 20 ml septa cap vial with THF (10 ml) added. To this was added 3-cyclohexyl-1-propanol (0.191 ml, 1.26 mmol), followed by triphenylphosphine (330 mg, 1.21 mmol). The reaction mixture was stirred at RT for 20 minutes and then DIAD (0.248 ml, 1.26 mmol) was added. The reaction mixture was stirred for 72 hours at RT, was then diluted with ethyl acetate (100 ml) and washed with saturated sodium bicarbonate (50 ml). The product was re-extracted with ethyl acetate (100 ml). The organic phases were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in dioxane (6 ml) and ethanol (6 ml). To this was added a 2.0M aqueous solution of LiOH (2.6 ml, 5.3 mmol). The reaction mixture was stirred at RT overnight, then was diluted with 30 ml of water and washed with ethyl acetate (2×50 ml) to remove any TPPO. The aqueous phase was adjusted to pH-2 with 1N HCl (10 ml) and the product was extracted with ethyl acetate (3×50 ml). The organic phases were combined, dried over sodium sulfate, filtered and concentrated to provide the title compound as a white solid (190 mg, 51%). MS (LC/MS) m/z 414.1 (M+1)1H NMR (400 MHz, METHANOL-d4) δ ppm 0.81-1.08 (m, 2H) 1.16-1.44 (m, 6H) 1.72 (s, 9H) 2.01 (s, 1H) 2.29-2.47 (m, 1H) 2.48-2.68 (m, 1H) 3.18 (s, 3H) 4.04 (s, 2H) 4.07-4.17 (m, 1H) 4.22-4.37 (m, 1H) 5.97-6.12 (m, 1H) 6.25-6.36 (m, 1H) 7.57-7.73 (m, 1H) added The reaction mixture was stirred for 72 hours at RT washed with saturated sodium bicarbonate (50 ml) The product was re-extracted with ethyl acetate (100 ml) dried over sodium sulfate filtered concentrated in vacuo The residue was dissolved in dioxane (6 ml) The reaction mixture was stirred at RT overnight washed with ethyl acetate (2×50 ml) to remove any TPPO the product was extracted with ethyl acetate (3×50 ml) dried over sodium sulfate filtered concentrated

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

实验步骤: Lithium aluminum hydride (24.2 g, 0.64 mole) was slurried into 300 ml of dry ether (distilled from benzophenone ketyl, generated in situ from sodium and benzophenone). The slurry was cooled in an ice-water bath and a solution of 100 g (0.64 mole) of 3-cyclohexylpropionic acid (Bielstein 9:[2]13) in 250 ml of dry ether was slowly added. The resultant mixture was heated to reflux for 1 hr and then cooled in an ice-water bath. Ethyl acetate (100 ml) was slowly added to the mixture. This addition was followed by the addition of 24.2 ml of water, 24.2 ml of 15% aqueous sodium hydroxide solution and 72.6 ml of water. The mixture was filtered and the solvent was removed in vacuo. Distillation of this mixture at reduced pressure resulted in 71.6 g (78.7%) of pure 3-cyclohexylpropan-1-ol having the following physical characteristics: The slurry was cooled in an ice-water bath to reflux for 1 hr cooled in an ice-water bath This addition The mixture was filtered the solvent was removed in vacuo Distillation of this mixture at reduced pressure resulted in 71.6 g (78.7%) of pure 3-cyclohexylpropan-1-ol having the following physical characteristics

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir: