1,1-Dimethylethyl 4-[4-amino-2-methyl-5-(1-methylethoxy)phenyl]-1-piperidinecarboxylate

Tert-Butyl 4- (5-isopropyl-2-methyl-4-nitrophenyl) -3, 6-dihydropyridine- 1 -carboxylate (22.6 g, 0.06 mol) , Palladium hydroxide on carbon (20percent w. T., 50percent aq., 2.26 g) was added to methanol (226 mL)and the reaction mixture was stirred at 30-40 ° C under hydrogen pressure (1MPa) for 5 hours. TLC indicated complete reaction, filtered, Solvent, to the residue by adding n-heptane, stirring at 0-10 degrees Celsius for 2 hours, filtration, the filter cake at 40-50 degrees Celsius vacuum drying in the white solid powder 4- (4-amino-5-isopropyl- Methylphenyl) -piperidine-1-carboxylic acid tert-butyl ester (19.9 g, yield: 95.0percent).Compound 13-c (3.15 g, 8.4 mmol) and 10percent palladium-carbon (0.5 g) were dissolved in methanol (10 mL).The reaction mixture was replaced with hydrogen three times and then hydrogenated at 40°C for 3 hours. The reactionmixture was filtered to remove palladium-carbon and the filtrate was concentrated under reduced pressure to deliver awhite solid 13-b (2.8 g, yield: 88percent). This product was used without further purification. LC-MS (ESI): m/z = 378 [M+H]+.Tert-butyl 4- (5-Isopropoxy-2-methyl-4-nitrophenyl) -5, 6-dihydropyridin-1 (2H) -carboxylate (0.715 g, 1.899 mmol)Was added at room temperature to tetrahydrofuran (10 mL)To the dissolved solution was added Pd / C (10.00percent, 0.101 g, 0.095 mmol)Hydrogen balloon was added, and the mixture was stirred at the same temperature for 48 hours. The reaction mixture was filtered through celite to remove solids.The solvent was removed under reduced pressure, and the concentrate was purified by column chromatography (SiO2, 12 g cartridge;Ethyl acetate / hexane = 10percent to 20percent) to give tert-butyl 4- (4-amino-5-isopropoxy-2-methylphenyl) piperidine-(0.545 g, 82.3percent) as a light orange liquid4-(2-methyl-4-nitro-5-isopropoxyphenyl)-5, 6-Dihydropyridine-1(2H)-carboxylic acid tert-butyl ester(668 mg) and 10percent Pd/C (7.5 mg) were added toStir in 40 ml of methanol overnight under a hydrogen atmosphere of 1 atm.The catalyst was removed by filtration, the filtrate was concentrated, and the residue was recrystallized from petroleum ether.The target product (brown oily liquid, 650 mg) was obtained.Step 2: Compound 2-3 (43.8 g, 161.0 mmol)Was dissolved in acetic acid (400.0 mL)And trifluoroacetic acid (25.0 mL)40percent platinum dioxide (17.6 g) was added, Nitrogen replacement, hydrogen, stirring for 5 minutes, Pressurized to 1 atmosphere, The reaction was carried out for 36 hours.After completion of the reaction, the mixture was cooled to room temperature, The organic phase was washed twice with 1.0 mol of saturated NaOH, dried over anhydrous sodium sulfate, concentrated and chromatographed on silica gel to give compound 2-4 (Example 2), and the residue was purified by silica gel column chromatography. 34.0 g), yield: 60.6percent.:_In Synthesis of Scheme 2, 'Synthesis of Compounds 2-4', the starting material 2-chloro-4-fluoro-5-nitrotoluene (i.e., 2-1), and the rest of the synthesis was carried out in the same manner as in Synthesis to give compound 2-4 in a yield of 62.8percent.

Molecular Weight:348.5
XLogP3:3.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:348.24129289
Monoisotopic Mass:348.24129289
Topological Polar Surface Area:64.8
Heavy Atom Count:25
Complexity:439
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes