ChemicalBook CAS DataBase List 4-Piperidinecarboxylic acid, 4-(phenylamino)-1-(2-phenylethyl)-, methyl ester

4-Piperidinecarboxylic acid, 4-(phenylamino)-1-(2-phenylethyl)-, methyl ester synthesis

9synthesis methods

Product Name:4-Piperidinecarboxylic acid, 4-(phenylamino)-1-(2-phenylethyl)-, methyl ester
CAS Number:61085-55-0
Molecular formula:C21H26N2O2
Molecular Weight:338.44

67-56-1 Synthesis

67-56-1
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4-Piperidinecarboxamide, 4-(phenylamino)-1-(2-phenylethyl)-

61085-40-3
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4-Piperidinecarboxylic acid, 4-(phenylamino)-1-(2-phenylethyl)-, methyl ester

61085-55-0
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Yield:61085-55-0 65%

Reaction Conditions:

with trifluorormethanesulfonic acid in dimethyl sulfoxide at 0; under 760.051 Torr; for 96 h;Reflux;

Steps:

Methyl 4-(phenylamino)-1-(2-phenylethyl)-4-piperidinecarboxylate (3)

Methanol (65 ml) was poured into a 250 ml round bottom flask and cooled to 0°C in an ice bath. Trifluorormethanesulfonic acid (11.5 ml) was added dropwise to the MeOH with intensive stirring and cooling (Caution: Very corrosive vapors and liquid Greatly exothermic process). After the addition of CF₃SO₃H was complete, the ice bath was removed and 2.2 ml DMSO was added, followed by the addition of 3.16 g amide (2).The reaction mixture was refluxed and monitored by TLC (DCM:MeOH, 8:1) until the starting material was mostly consumed (after about 4 days of refluxing), about 90% conversion. The reaction mixture was cooled down to room temperature and slowly poured into 300 ml of 10% aqueous K₂CO₃. The mixture was transferred to a separatory funnel and the product was extracted with 6 x 50 ml EtOAc. Combined extracts were washed with 2 x 50 ml aq. NaHCO₃ solution, followed by drying over anhydrous Na₂SO₄ and removal of the volatiles under reduced pressure. The obtained crude product was purified by flash chromatography on silica gel with DCM:EtOAc:iPrOH 6:2:1. Methyl 4-(phenylamino)-1-(2-phenylethyl)-4-piperidinecarboxylate (2.09 g) was obtained in 65% yield as a creamy white solid, mp. 92-94°C, lit.⁶ mp. 94.9 C; Rf=0.5; ¹H NMR (700 MHz, CDCl₃) d: 2.08 (d, J14.0 Hz, 2H, CH₂), 2.30(t, J10.5 Hz, Ph-CH₂-CH₂-N, 2H), 2.54 (t, J10.5 Hz, Ph-CH₂-CH₂-N, 2H), 2.64 -2.66 (m, 2H, CH₂), 2.73 (s, CH₂, 2H), 2.81-2.83 (m, CH₂, 2H), 3.69 (s, COOCH₃, 3H),3.87 (s, NH, 1H), 6.58 (d, J 8.4 Hz, Ar(H), 2H), 6.76 (t, J 7.7 Hz, Ar(H), 1H), 7.14- 7.16 (m, Ar(H), 2H), 7.19 - 7.21 (m, Ar(H), 3H), 7.25 - 7.29 (m, Ar(H), 2H). ¹³CNMR (125 MHz, CDCl₃) d: 32.86, 33.56, 48.99, 52.36, 58.17, 60.30, 115.51, 118.87,126.16, 128.45, 128.69, 129.17, 139.99, 144.85, 175.68.