With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.25504-47-6,Methyl 2-oxopiperidine-4-carboxylate,as a common compound, the synthetic route is as follows.
To a stirred solution of compound 1 (2 g, 12.7 mmol) in THF (15 mL) was added LiHMDS (1.0 M solution in THF, 38.2 mL, 38.2 mmol) slowly at -78 ¡ãC under nitrogen atmosphere. The reaction temperature was raised to -40 ¡ãC and stirred for 1 h. Int-A (3.2 g, 14.0 mmol) in THF (5 mL) was added drop wise at -78 ¡ãC. The reaction mixture was brought to room temperature and stirred for 2 h. After consumption of the starting material (by TLC), the reaction was quenched with aqueous NH4Cl (30 mL) and extracted with CH2CI2 (2 x 100 mL). Organic layer was dried over Na2S04and concentrated under reduced pressure. The crude material was purified by column chromatography by eluting with 5percent MeOH/ CH2CI2 to afford a mixture of AK & AL (2.8 g, 66percent) as brown syrup. Mixture of AK & AL (1 g) was purified by chiral preparative HPLC purification to obtain AK (270 mg) as light brown solid and AL (256 mg) as an off white solid.AK:NMR (400 MHz, DMSO-d6) delta 7.55 (br s, 1H), 6.90 (d, J = 8.5 Hz, 1H), 6.79 (d, J = 8.5 Hz, 1H), 4.32 – 4.16 (m, 2H), 3.78 (d, J = 2.4 Hz, 6H), 3.74 (s, 3H), 3.30 – 3.24 (m, 1H), 3.17 – 3.12 (m, 1H), 3.07 (d, J = 5.6 Hz, 1H), 2.97 (d, J = 5.6 Hz, 1H), 2.34 (s, 2H), 1.98 – 1.77 (m, 2H) LCMS (ESI): m/z 335.2 [M++l]HPLC: 99.71percentChiral HPLC: >99.00percentColumn : CHIRALPAK IC (250*4.6 mm*3qm)Mobile Phase : A: 0.1percent DEA in n-HexaneMobile Phase : B: DCM : MeOH (50 : 50)A : B :: 65 : 35; Plow rate : 1.0 mL/minRetention time : 21.285 minAL:NMR (400 MHz, DMSO-d6) delta 7.55 (br s, 1H), 6.90 (d, J = 8.7 Hz, 1H), 6.79 (d, J = 8.7 Hz, 1H), 4.33 – 4.17 (m, 2H), 3.78 (d, J = 2.6 Hz, 6H), 3.74 (s, 3H), 3.30 – 3.24 (m, 1H), 3.17 – 3.12 (m, 1H), 3.07 (d, J = 5.5 Hz, 1H), 2.97 (d, J = 5.5 Hz, 1H), 2.34 (s, 2H), 1.94 – 1.78 (m, 2H) LCMS (ESI): m/z 335.2 [M++l]HPLC: 99.74percentChiral HPLC: 998.10percentColumn : CHIRALPAK IC (250*4.6 mm* 3 pm)Mobile Phase : A: 0.1percent DEA in n-HexaneMobile Phase : B: DCM : MeOH (50 : 50)A : B :: 65 : 35; Plow rate : 1.0 mL/minRetention time : 24.308 min, 25504-47-6
The synthetic route of 25504-47-6 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; APTINYX INC.; KHAN, M., Amin; (87 pag.)WO2019/152685; (2019); A1;,
Piperidine – Wikipedia
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