Olmesartan medoxomil key intermediate, synthesis method thereof and method for synthesizing olmesartan medoxomil from same
A technology of olmesartan medoxomil and a synthesis method, which is applied in the field of chemical synthesis, can solve the problems of long synthesis route and increase the difficulty of industrialization, and achieves the effects of simple operation, less side reactions and high yield
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Embodiment 1
[0035] Example 1: Preparation of 4,4-dimethyl-2-propyl-4,6-dihydrofuro[3,4-d]imidazole-6-hydroxyl (III).
[0036]Anhydrous tin dichloride (0.03mol) and diethyl ether (100mL) were placed in a three-neck flask equipped with a calcium chloride drying tube condenser and a mechanical stirrer, and dry hydrogen chloride gas was introduced, and the mixed solution was slowly stirred until the solid was completely disappear. After stopping the flow of hydrogen chloride, 4-(1-hydroxy-1-methylethyl)-2-propylimidazol-5-cyano(I) (2.9 g, 0.015 mol) was quickly dropped in and vigorously stirred for 1 h. The mixture was allowed to stand until the solid-liquid separation was complete, the supernatant was poured out, the residue was washed with ether (30ml×2), water (80ml) was added to the remaining solid, and the pH was adjusted to neutral with sodium bicarbonate. The mixture was distilled, and the distillation was stopped when the volume of the distillate was about 50ml. The distillate was ex...
Embodiment 2
[0039] Example 2: Preparation of 4,4-dimethyl-2-propyl-4,6-dihydrofuro[3,4-d]imidazole-6-hydroxyl (III).
[0040] Dissolve 4-(1-hydroxyl-1-methylethyl)-2-propylimidazolium-5-cyanide (I) (2.9g, 0.015mol) in 30ml of anhydrous dichloromethane, N 2 Under protection, DIBAL-H (0.015mol) was slowly added dropwise at room temperature, and the addition was completed in 30 minutes. The solution turned slightly yellow, kept at the temperature for 2h, TLC to no raw material. Add saturated ammonium chloride solution (20ml) dropwise at room temperature. At this time, the solution slowly becomes cloudy. After the addition, continue to stir for 0.5 hours, then add ethyl acetate (30ml) and continue to stir for 1 hour. Separate the organic layer, and wash the aqueous layer with acetic acid Ethyl ester (20ml×2) was extracted, the organic layers were combined, dried over anhydrous magnesium sulfate, filtered, and the organic solvent was spinned out under reduced pressure to obtain a light yellow...
Embodiment 3
[0043] Example 3: Preparation of 4,4-dimethyl-2-propyl-4,6-dihydrofuro[3,4-d]imidazole-6-hydroxyl (III).
[0044] Dissolve 4-(1-hydroxy-1-methylethyl)-2-propylimidazol-5-cyanide (I) (2.9g, 0.015mol) in 50ml of absolute ethanol, add 0.3g of Raney nickel, Add 1ml of formic acid dropwise, and react with hydrogen at normal temperature and pressure until no hydrogen is absorbed. After the reaction was completed, filter, and the oily product 4,4-dimethyl-2-propyl-4,6-dihydrofuro[3,4-d]imidazole-6-hydroxyl (III) was concentrated and dried in the filtrate, and the yield was 79%, the detection parameters are as follows:
[0045] 1 H NMR (300MHz, CDCl 3 +D 2 O) δppm: 0.95 ~ 1.03 (3H, t, CH 3 CH 2 CH 2 ), 1.64~1.76 (6H, s, 2 CH 3 ), 1.83~1.95 (2H, m, CH 3 CH 2 CH 2 ), 2.35~2.55 (2H, m, CH 3 CH 2 CH 2 ).
[0046] MS (FAB, m / z): 195 (M + +1).
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