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A technology of compounds and hydrates, applied in the directions of active ingredients of heterocyclic compounds, digestive system, organic chemistry, etc., can solve the problems of no effect and reducing food intake.
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Embodiment 1
[0192] Cyclopentylcarbamate (1-methylpiperidin-4-yl)methyl ester hydrochloride
[0193]
[0194] (1-Methylpiperidin-4-yl)methanol (Intermediate 2; 4.67 g, 35.7 mmol) was dissolved in anhydrous THF (40 mL) and cyclopentyl isocyanate (3.62 mL, 32.1 mmol) was added . After stirring at room temperature for 16 hours, the reaction mixture was concentrated in vacuo. The residue was dissolved in hot EtOAc (5 mL), cooled to 0 °C, filtered, and the filtrate was concentrated in vacuo. A 60% fraction of the crude product was purified by normal phase chromatography (gradient elution from 0% to 10% MeOH / DCM with 1% NH 3 aqueous solution). The residue was dissolved in acetonitrile (20 mL), 2M HCl in Et was added 2 O (3 mL, 6 mmol) solution, and the solution was concentrated in vacuo. The residue was dissolved in 2M aqueous HCl (25 mL), washed with EtOAc (3 x 25 mL), filtered and dried in vacuo to give (1-methylpiperidin-4-yl)methyl cyclopentylcarbamate hydrochloride (1.32 g, 25%), a...
Embodiment 2
[0197] (1-Phenylcyclopentyl)carbamate (1-methylpiperidin-4-yl)methyl formate
[0198]
[0199] (1-Methylpiperidin-4-yl)methanol (Intermediate 2; 0.430 g, 2.0 mmol) and 1-phenylcyclopentyl isocyanate (0.445 g, 2.0 mmol; according to Kaiser, C. and Weinstock J. , Org. Synth. Coll., Vol. 7, prepared by the procedure described in 433) was dissolved in anhydrous toluene (5 mL) and heated at reflux for 2 hours, after which time the volatiles were removed in vacuo. The residue was dissolved in MeOH (3 mL), concentrated in vacuo, and purified by reverse phase chromatography (gradient elution with MeOH / water, 1% formic acid in each solvent, 0% to 100%) to afford (1-benzene (1-methylpiperidin-4-yl)carbamate (110 mg, 15%), a clear oil.
[0200] Analytical LCMS: purity 98.9% (system C, R T =5.93min), ES + : 317.1[MH] + ; HRMS: C 19 h 28 N 2 o 2 Calculated value: 316.2151, measured value: 316.2158.
Embodiment 3
[0202] Bicyclo[2.2.1]hept-2-ylcarbamate (1-methylpiperidin-4-yl)methyl ester hydrochloride
[0203]
[0204] To a solution of bis-4-nitrophenyl carbonate (7.06 g, 23.2 mmol) in DCM (100 mL) was added successively (1-methylpiperidin-4-yl)methanol (Intermediate 2; 2.50 g, 19.3 mmol ) in DCM (50 mL) and NMM (1.70 mL, 15.5 mmol). The reaction mixture was stirred for 90 h, concentrated in vacuo, and the residue was dissolved in EtOAc (80 mL), then washed with 1M Na 2 CO 3 Wash with aqueous solution to remove p-nitrophenol. dry (MgSO 4 ) organic layer and evaporated in vacuo to give (1-methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate (4.18 g, 73%) as a yellow solid.
[0205] Analytical LCMS: (system A, R T =1.59min), ES + : 295.1[MH] + .
[0206] To a solution of (1-methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate (587 mg, 2.0 mmol) in DMF (20 mL) was added DIPEA (0.696 mL, 2.0 mmol), DMAP (10 mg, catalytic) and exo-2-aminonorbornane (0.356 mL, 3.0 mmol). The reac...
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