3-Amino-1-adamantanol

White solid

To a round bottom flask containing 1, amantadine hydrochloride (100 mg, 0.53 mmol) a mixture of concentrated sulfuric acid (2 ml, 37.1 mmol) andconcentrated nitric acid (0.2 ml, 4.46 mmol) was added at 0To an ice-cooled mixture of sulfuric acid (96percent, 12.33 mL, 231 mmol) and nitric acid (65percent, 1.2 mL, 26.5 mmol) was added 1-aminoadamantane hydrochloride (1 g, 6.61 mmol) portion wise. The mixture was stirred at rt for 2 days, ice-water (6 mL) was added to the reaction mixture. The solution was stirred in an ice-water bath for 30 min; KOH (35 g, 0.62 mol) was added in small portions over 1 h at such a rate to keep the temperature below 80 °C. The resulting white paste was mixed with CHTo an ice-cooled mixture of sulfuric acid 96percent (12.33 mL, 231 mmol) and nitric acid 65percent (1.2 mL, 26.5 mmol) was added 1-aminoadamantan HCl (1g, 6.61 mmol) portionwise. 38 ml of 98percent concentrated sulfuric acid with 4 ml of 65percent concentrated nitric acid in mixed under ice bath cooling, the mixed acid in to the adding 3 . 75 g amantadine hydrochloride, stirring in ice bath reaction 3 hours; 60 g adding crushed ice, stirring 0.5 hours; then adding solid potassium hydroxide, to adjust the pH value to 12 - 13, the reaction under ice bath 2 hours; and filtering, the filtrate concentrated hydrochloric acid to adjust the pH value to 8 - 9, concentrated to dry; adding 80 ml anhydrous ethanol reflux 1 hour, cool, filtered, the filtrate is concentrated to dry; then adding 10 ml of the mixed liquid (acetone: ethyl acetate=3:1) reflux 1 hour, placed under ice bath, filtered, shall be 3 - amino adamantanol mellow solid 3.2 g, (1) To a three-mouth flask, equipped with thermometer and tail gas absorption device, add 170 ml trifluoroacetic acid, and 800 ml fuming sulfuric acid. Under ice-bath cooling, under stirring slowly drop 56 ml 65percent concentrated nitric acid, stirring 30min, When temperature drop to 0 °C, in 30min divided 8 times add 76g amantadine hydrochloride, After stirring 3 hours, remove ice-bath. Control temperature to 20 °C, stirring 10 hours, to the reaction solution is added to the reaction solution in the ice cubes one by one for clarification, the reaction liquid is moved to the stirring in ice bath 30min, after the reaction liquid into white, removed ice, stirring under batchwise by adding 89percent potassium hydroxide to neutralize, to the solution is strongly alkaline to continue after the stirring, the absorption of the generation of a white solid;Preparation of 3-amino-adamantan-l-ol (0099) In a clean and dry 5.0 L 4 necks RBF equipped with liquid addition funnel, TP. Charged cone, sulphuric acid (300 mL, 2 V) and cooled the reaction mass to 5-10 °C. To the cooled mass 1-adamantyl amine (150 g, 1 eq.) was added lot wise at 5-10 °C. After complete addition, stirred the reaction mass to get clear (slightly hazy) solution and maintained the reaction mass at 5-15 °C. Meanwhile a nitrating mixture was prepared by adding 150 mL of 65-70 percent nitric acid to 450 mL cone, sulphuric acid maintaining temperature at 0-10 °C). The nitrating mixture was added to the reaction mass maintaining reaction temperature at 20 ± 5 °C. After the addition was over, stirred the reaction mass at 20 ± 5°C for 3 to 5 h. Completion of the reaction was confirmed by GC. The reaction mass was cooled to 0 - 5 °C and added water (150 mL, I V) to the reaction mass maintaining 0-20 °C and again cooled reaction mass to 5-10 °C. Second lot of water (300 mL, 2 V) was added to the reaction mass maintaining 5-20 °C. The reaction mass was cooled again to 5-10 °C and added third lot of water (1050 mL, 7 V) to the reaction mass maintaining 5-20 °C. After complete addition of water the reaction mass was cooled to 0-5 °C and added 50 percent NaOH solution maintaining 0- 40 °C and stirred for 1 h at 35-40 °C. Filtered the solid obtained and washed the cake with water (150 mL, IV). Wet weight: 1 185 g. The wet cake was dried under reduced pressure at 60-70 °C. Mixed the above dried solid with IPA (750 mL, 5 V w.r.t. adamantly amine) and heated at 50 - 60°C and maintained for 1 h. Then cooled reaction mass to 20-25°C and maintained at 20-25°C for 1 h. Filtered the solid obtained and wash with IPA (150 mL, 1 V). Distilled around 600 mL, 4 - 4.5 V of IPA from reaction mass under reduced pressure and cooled the residual reaction mass to 40-45°C. Added cyclohexane (1200 mL, 8 V) to reaction mass and heated to 50-55°C. Applied 200-250 Torr vacuum slowly to the reaction mass and distilled cyclohexane (900 mL, 6 V) from reaction mass under reduced pressure. Filtered the solid and wash with cyclohexane (150 mL, IV) Unload solid and dry it for 10-12 h under reduced pressure at 60°C. Yield range: 90percent; GC purity > 98percent; melting point: 265°C; 1H NMR (CDC1To a round bottom flask containing compound 13 (100mg, 0.53mmol) a mixture of concentrated sulfuric acid (2mL, 37.1mmol) and concentrated nitric acid (0.2mL, 4.46mmol) was added at 0°C. The mixture was left to stir for two hours at 10°C. Ice-cold water was then carefully added to the reaction mixture, following this addition the reaction mixture was made basic using solid sodium hydroxide until precipitation could be seen. The solution was thereafter filtered, and the wet solid collected and dissolved in DCM and left to stir for 30min. Next, the solid was removed from the solution by filtration and washed with DCM. The DCM-solution containing 14 was concentrated in vacuo to afford compound 14 (70mg, yield 81percent). Added in the reaction bottle 96percent - 98percent concentrated sulfuric acid 300 ml (5.28mol) stirring cooling to 5 °C the following, is dripped slowly into the 68percent nitric acid 30 ml (0.41mol), and ice in batches under cooling by adding amantadine hydrochloride 24g (0.13mol). The temperature is increased to 25 °C stirring reaction 10hr. Lowering the temperature to the reaction liquid 15 °C the following, under stirring sodium methoxide methanol solution slowly adding 400 ml (25percent, 1 . 80mol), pH > 14, the 30 °C stirring for 30 min, solid inorganic salt worry eliminates, filtrate water 100 ml, stirring and heating to reflux 1hr, filtering, the filtrate concentrated under reduced pressure, obtaining white crystalline 3-hydroxy-1-amantadine (2) (19.5g, 89.4percent).

Employed in the synthesis of inhibitors with antihyperglycemic properties.1

Molecular Weight:167.25
XLogP3:0.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:167.131014166
Monoisotopic Mass:167.131014166
Topological Polar Surface Area:46.2
Heavy Atom Count:12
Complexity:212
Undefined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes