8-Benzyl-8-azabicyclo[3.2.1]octan-3-one

Off-White to Pale Yellow Low-Melting Solid

Concentrated hydrochloric acid (30 mL) was added to a heterogeneous solution of 2, 5-dimethoxy tetrahydrofuran (82.2 g, 0.622 mol) in water (170 mL) while stirring. Preparation of 8-Benzyl-8-aza-bicyclo[3.2.1]octan-3-one; A solution of 2, 5-dimethoxy tetrahydro furan (15 g, 113 mmol) in 1N HCI (250 mL) was heated to 70A solution of 2, 5-dimethoxytetrahydrofuran (19.8 g, 149.8 mmol) in 0.1M hydrochloric acid (180 ml, 18.0 mmol) was stirred at 80°C for 2 hours. The reaction solution was cooled to 0°C, acetonedicarboxylic acid (19.8 g, 149.8 mmol), concentrated hydrochloric acid (13.8 ml, 164.8 mmol), sodium acetate (14.8 g, 179.8 mmol), and benzylamine (17.7 g, 164.8 mmol) were added to the reaction solution, and the mixture was stirred at the same temperature for 12 hours and at 55°C for 2 hours. The reaction solution was cooled to room temperature, and an aqueous solution of 4M sodium hydroxide (70 ml) was added, followed by extraction with chloroform. The organic layer was dried over sodium sulfate and then concentrated under a reduced pressure. The residue was purified by flash chromatography (silica gel, n-hexane/ethyl acetate) to give a title compound (23.3 g, 108 mmol, 72percent) as a light yellow oil product. Step 1:Intermediate I-25 (8-benzyl-8-azabicyclo[3.2.1]octan-3-one)Concentrated hydrochloric acid (3 mL) was added to a stirred suspension of intermediate I-24 (8.2 g, 62 mmol, 1 eq) in water (17 mL), the reaction mixture was stirred for additional 20 minutes and diluted with water (25 mL). In a separate flask cooled to 0° C. on an ice bath, concentrated hydrochloric acid (9 mL) was added slowly to a solution of benzyl amine (10 g, 93 mmol, 1.5 eq) in water (35 mL), and this solution was added to the above solution of I-24. A solution of 1, 3-acetonedicarboxylic acid (10 g, 68 mmol, 1.1 eq) in water (40 mL) was added followed by a solution of sodium hydrogen phosphate (4.4 g, 31 mmol, 5.0 eq) in water (20 mL). The acidity was adjusted from pH 1 to pH 4.5 using a solution of NaOH (40percent in water). The resulting cloudy and pale- yellow solution was stirred overnight at room temperature. The reaction mixture was acidified to pH 3 from pH 7.5 using aqueous HCl solution (50percent in water) and stirred at 85° C. for 2 hours. The crude reaction mixture was cooled to room temperature, basified to pH 12 using a solution of NaOH (40percent in water) and extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSOUnder NTo a solution of 0.025 M aqueous hydrochloric acid (100 ml) at [0°C] was added 2, [5-DIMETHOXY-TETRAHYDROFURAN] (30 ml 231 [MMOL).] The reaction was stirred at [0°C] overnight. The reaction was then diluted with water (200 ml) and benzyl amine hydrochloride (40 grams, 278 [MMOL), ] 3-oxo-pentanedioic acid (33.7 grams, 231 [MMOL), ] and sodium acetate (10.7 grams, 130 [MMOL)] were added. The reaction was stirred for 5 minutes at [0°C, ] warmed to ambient temperature and stirred for 90 minutes, then heated to [50°C] for two hours, cooled to [0°C] and basified to pH = 10 with 50 [percent] aqueous sodium hydroxide (14 [ML).] The reaction mixture was extracted with ethyl acetate (3 times) and the organic layers were combined and washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo to give a brown oil. Silica gel chromatography gave the title compound (33.46 grams, 67 percent yield8-Benzyl-8-Aza-Bicyclo[3.2.1]Octan-3-One 8-Benzyl-8-aza-bicyclo[3.2.1]octan-3-one Following the procedure described in example 1, 57 ml of 2.5-dimethoxy-tetrahydrofuran (0.440 moles) in 64 ml of water and 0.12 ml of HCl are reacted with 62.9 g of acetonedicarboxylic acid (0.431 moles), 44 g of tribasic sodium citrate bihydrate (0.149 moles) in 64 ml of water, 25 g of ice and 48.15 g of benzylamine (0.450 moles) to give the required product.

An intermediate for the preparation of β-Cocaine, opioid receptor antagonists, and CCR-5 receptor antagonists

Molecular Weight:215.29
XLogP3:1.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:215.131014166
Monoisotopic Mass:215.131014166
Topological Polar Surface Area:20.3
Heavy Atom Count:16
Complexity:254
Undefined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes