* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With hydrogen;palladium(II) oxide; In methanol; water; at 20℃; under 3750.38 Torr;
13a Perhydro-azepin-3-oneTo 120 g (500 mmol) <strong>[146407-32-1]1-benzyl-perhydro-azepin-3-one</strong> in 800 mL MeOH and 100 mL water is added 12.0 g Pd(II)-O. The reaction mixture is stirred under a hydrogen atmosphere of 5000 hPa at RT overnight. The solvent is evaporated, the residue is co-evaporated twice with 100 mL toluene. The residue is elutriated with acetone. The precipitate is collected and dried. Yield: 73.5 g (98% of theory) <n="89"/>Melting point = 142CRf-value: 0.55 (silica gel, mixture H).
With hydrogenchloride; for 12h;Reflux; Inert atmosphere;
Compound 53-3 (18 g, 65.5 mmol) was added into HCl solution (6 mol/L, 180 mL) under nitrogen atmosphere, and the reaction solution was stirred at reflux for 12 h. After TLC indicated the reaction was complete, the reaction solution was cooled down to r.t. and adjusted to a pH greater than 9 with NaOH solution. The resulting solution was extracted with a mixture of DCM/MeOH (10/1) (200 mL×2). The organic phase was washed with saturated brine, dried over anhydrous Na2SO4, filtered and evaporated to give the title compound 53-4 (yellow oil, 11.9 g, Yield 89%). 1H NMR (400 MHz, d6-DMSO): delta ppm 7.38-7.27 (m, 5H), 3.72 (s, 2H), 3.27 (s, 2H), 2.76-2.71 (m, 4H), 1.75 (m, 4H)
With sulfuric acid; In ethanol; water; at 120℃; for 12h;
Under a nitrogen atmosphere, a 75%-aqueous sulfuric acid solution (2 ml) was added to a solution of ethyl 1-benzyl-3-oxoazepane-4-carboxylate (150 mg, 0.545 mmol) in ethanol (1 ml) at room temperature, and the resulting mixture was heated to 120C. After 3 hours, completion of the reaction was confirmed and the resulting mixture was cooled. On the other hand, under a nitrogen atmosphere, a 75%-aqueous sulfuric acid solution (2 ml) was added to a solution of the mixture containing ethyl 1-benzyl-3-oxoazepane-2-carboxylate (200 mg, content = about 75%) in ethanol (1 ml) at room temperature, and the resulting mixture was heated to 120C. After 12 hours, completion of the reaction was confirmed and the temperature was lowered. The reaction solution was combined with that obtained above, and the combined reaction solution was poured onto ice and adjusted to pH 8 with a 2M-aqueous sodium hydroxide solution. The combined reaction solution thus treated was extracted with ethyl acetate (50 ml x 2) and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain 1-benzylazepan-3-one (118.1 mg, 53%).
With lithium aluminium tetrahydride; In diethyl ether; at 20℃; for 0.5h;
Under a nitrogen atmosphere, lithium aluminum hydride (1.4 mg, 0.0369 mmol) was added to a solution of <strong>[146407-32-1]1-benzylazepan-3-one</strong> (15 mg, 0.0738 mmol) in diethyl ether (1 ml) at 0C, and the resulting mixture was heated to room temperature. After 30 minutes, water, a 2M-aqueous sodium hydroxide solution and water were added in that order to the reaction solution. The resulting mixture was filtered by the use of Celite, and the filtrate was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol) to obtain 1-benzylazepan-3-ol (16.2 mg, 100%).
With sulfuric acid; In ethanol; water; at 120℃; for 3h;
Under a nitrogen atmosphere, a 75%-aqueous sulfuric acid solution (2 ml) was added to a solution of ethyl 1-benzyl-3-oxoazepane-4-carboxylate (150 mg, 0.545 mmol) in ethanol (1 ml) at room temperature, and the resulting mixture was heated to 120C. After 3 hours, completion of the reaction was confirmed and the resulting mixture was cooled. On the other hand, under a nitrogen atmosphere, a 75%-aqueous sulfuric acid solution (2 ml) was added to a solution of the mixture containing ethyl 1-benzyl-3-oxoazepane-2-carboxylate (200 mg, content = about 75%) in ethanol (1 ml) at room temperature, and the resulting mixture was heated to 120C. After 12 hours, completion of the reaction was confirmed and the temperature was lowered. The reaction solution was combined with that obtained above, and the combined reaction solution was poured onto ice and adjusted to pH 8 with a 2M-aqueous sodium hydroxide solution. The combined reaction solution thus treated was extracted with ethyl acetate (50 ml x 2) and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain 1-benzylazepan-3-one (118.1 mg, 53%).
Eine Suspension von Kalium tert-Butylat (336 mg) in Toluol (2. 5 ml) wird waehrend 10 min am Rueckfluss gekocht. Anschliessend wird 5- (BENZYL-ETHOXYCARBONYLMETHYL-AMINO)- pentansaeure (695 mg) in Toluol (1 ml) langsam zur Suspension gegeben und nach beendeter Zugabe waehrend 1. 5 Stunden weiter gekocht. Nach Abkuehlen auf Raumtemperatur wird 25% Chlorwasserstoffsaeure (1 ml) zugegeben. Die organische Phase wird abgetrennt und mit 25% Chlorwasserstoffsaeure (4x 1 ml) gewaschen. Die vereinigten salzsauren waessrigen Phasen werden anschliessend waehrend 5 Stunden am Rueckfluss gekocht. Nach Abkuehlen auf Raumtemperatur wird die Loesung mit 2N Natronlauge basisch (pH 11) gestellt und mit Ethylacetat extrahiert. Die vereinigten organischen Phasen werden nach dem Trocknen ueber Natriumsulfat eingedampft. Der erhaltene Rueckstand ergibt nach Chromatographie an Kieselgel (Ethylacetat/ Heptane 1 : 5) und ergibt die gewuenschte Titelverbindung (197 mg) in 45 % Ausbeute (Bull. Chem. Soc. JPN. 1956, 29, 631- 632 ; DE2206385).
ethyl (1-benzylazepane-3-ylidene)acetate[ No CAS ]
ethyl (1-benzylazepane-3-ylidene)acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 2h;
Sodium hydride and <strong>[146407-32-1]1-benzylazepane-3-one</strong> were added to a THF solution of ethyl diethoxyphosphorylacetate under ice cooling and stirred for two hours at room temperature to give a stereoisomeric mixture of ethyl (1-benzylazepane-3-ylidene)acetate. After the obtained stereoisomeric mixture of ethyl (1-benzylazepane-3-ylidene)acetate was processed with 4M HCl-EtOAc solution, EtOH and 10% palladium carbon were added and stirred for 15 hours at room temperature under the hydrogen atmosphere to give ethyl azepane-3-ylacetate hydrochloride. MS: 186
ethyl (1-benzylazepane-3-ylidene)acetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium hydride; In tetrahydrofuran; ethanol; at 0 - 20℃; for 2h;
Reference Example 10 Sodium hydride and <strong>[146407-32-1]1-benzylazepan-3-one</strong> were added to a THF solution of ethyl diethoxyphosphorylacetate with ice-cooling, and the mixture was stirred at ambient temperature for 2 hours to yield a stereoisomeric mixture of ethyl (1-benylazepan-3-ylidene)acetate, which was treated with 4M HCl-EtOAc solution, followed by adding EtOH and 10% palladium on activated carbon and stirring under hydrogen atmosphere at ambient temperature for 15 hours to yield ethyl azepan-3-ylacetate hydrochloride. MS:186
With recombinant Rhodococcus erythropolis DSM 43297 ketoredutase; nicotinamide adenine dinucleotide; In aq. phosphate buffer; isopropyl alcohol; at 50℃; for 24h;pH 7.0;Enzymatic reaction;
General procedure: The reaction mixture containing 200 mM substrate, 1mM NAD+, 5% (v/v) 2-propanol and 10mg crude enzyme READH in 1mL potassium phosphate buffer (100mM, pH 7.0) was incubated at 50 C. For ChKRED20, 40% (v/v) 2-propanol and a reaction temperature of 40 C were applied instead. The reaction was monitored by TLC, and terminated by extracting with methyl tert-butyl ether (1 mL). The organic extract was dried over anhydrous sodium sulfate and concentrated. The samples were subjected to chiral HPLC to determine the conversion and enantiomeric excess. The products were purified by silica gel column chromatography, and identified by NMR analysis, optical rotation measurements and mass spectrometry.
With recombinant Chryseobacterium sp. CA 49 ketoreductase; nicotinamide adenine dinucleotide; In aq. phosphate buffer; isopropyl alcohol; at 40℃; for 24h;pH 7.0;Enzymatic reaction;
General procedure: The reaction mixture containing 200 mM substrate, 1mM NAD+, 5% (v/v) 2-propanol and 10mg crude enzyme READH in 1mL potassium phosphate buffer (100mM, pH 7.0) was incubated at 50 C. For ChKRED20, 40% (v/v) 2-propanol and a reaction temperature of 40 C were applied instead. The reaction was monitored by TLC, and terminated by extracting with methyl tert-butyl ether (1 mL). The organic extract was dried over anhydrous sodium sulfate and concentrated. The samples were subjected to chiral HPLC to determine the conversion and enantiomeric excess. The products were purified by silica gel column chromatography, and identified by NMR analysis, optical rotation measurements and mass spectrometry.
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