Amlodipine Impurity 28 synthesis

9synthesis methods

Product Name:Amlodipine Impurity 28
CAS Number:79781-21-8
Molecular formula:C18H20ClNO5
Molecular Weight:365.81

ethyl 2-acetoxymethyl-4-(2-chlorophenyl)-1,4-dihydro-5-methoxycarbonyl-6-methyl-3-pyridinecarboxylate

144686-65-7
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Yield:79781-21-8 65%

Reaction Conditions:

with ammonia in methanol at 0; for 2 h;

Steps:

11.E

Intermediate E: 3-Ethyl 5-methyl 4-(2-chlorophenyl)-2-(hydroxymethyl)-6-methyl-1 ,4- dihydropyridine-3,5-dicarboxylate. To a solution of intermediate D (1 .2 g, 2.9 mmol, 1 .0 eq) in methanol (20 mL) was added a methanolic ammonia solution (1 .0 M, 15 mL, 15 mmol). The mixture was stirred at 0 °C for 2 h then the solvent was removed under reduced pressure and the residue was diluted with water (50 mL). The aqueous mixture was extracted with CH₂CI₂ (50 mL x 3) and the combined organic layers were washed with brine (60 mL x 2), dried over MgS0₄ and concentrated under reduced pressure. The residue was purified by flash chromatography (Pet. ether/EtOAc, 1 /10 to 1 /2, v/v) to give 3-ethyl 5-methyl 4-(2-chlorophenyl)-2-(hydroxymethyl)-6-methyl-1 ,4- dihydropyridine-3,5-dicarboxylate (0.70 g, 65%) as a yellow solid.LC-MS (Agilent): R_t 3.28 min; m/z calculated for Ci₈H₂₀CINO₅ [M+H]⁺ 366.1 , [M+Na]⁺ 388.1 , found [M+H]⁺ 366.1 , [M+Na]⁺ 388.1 .¹H NMR: (400 MHz, CDCI₃) δ (ppm): 7.39 (m, 1 H), 7.25 (m, 1 H), 7.13 (m, 1 H), 7.05 (m, 1 H), 5.41 (s, 1 H), 4.75 (d, J = 4.4 Hz, 2H), 4.06 (m, 2H), 3.63 (s, 3H), 2.33 (s, 3H), 1 .20 (t, J = 7.2 Hz, 3H).