Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 1139-13-5, name is Diethyl cyclohexane-1,1-dicarboxylate, A new synthetic method of this compound is introduced below., COA of Formula: C12H20O4
Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps, and cheap raw materials. 1139-13-5, name is Diethyl cyclohexane-1,1-dicarboxylate, A new synthetic method of this compound is introduced below., COA of Formula: C12H20O4
Example 9 Preparation of 1-fluoromethylcvclohexylalanine P2 building block Cyclohexane-1,1-dicarboxylic acid diethyl ester,1 , was prepared in accordance with JACS 43, 1921, 1368 from diethyl malonate and 1 ,5-dibromopentane.Cyclohexane-1,1-dicarboxylic acid diethyl ester, 1 , was taken up in anhydrous THF under nitrogen at room temperature. This was treated with LiAI(O1Bu)3H (2.5eq) portionwise before refluxing overnight. The reaction mixture was cooled in an ice-bath and treated carefully with 10% KHSO4(aq) and allowed to stir for 10 minutes. The resulting precipitate was removed by vacuum filtration and the mother liquors were partitioned between EtOAc and brine. The organic phases were combined, dried over MgS04, filtered and concentrated in vacuo to give a mobile oil. This was purified by flash column chromatography to give 1-hydroxymethyl- cyclohexanecarboxylic acid ethyl ester, 2 as a colourless oil (51%). EPO 1-Hydroxymethyl-cyclohexanecarboxylic acid ethyl ester, 2 was taken up in [bis (2- methoxyethyl) amino] sulphur trifluoride and heated overnight at 7O0C. The reaction was then allowed to cool to O0C and carefully treated with saturated NaHCO3 (aq) dropwise. This was stirred at room temperature for 30 minutes. The mixture was washed twice with DCM and the combined organics were washed with saturated NaHCO3 (aq) and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography to give 1 -fluoromethyl-cyclohexane carboxylic acid ethyl ester, 3, as a colourless oil (34%)1-Fluoromethyl-cyclohexane carboxylic acid ethyl ester, 3, was dissolved in anhydrous THF and cooled under a nitrogen atmosphere to O0C. This was treated portionwise with LiAIH4 (2eq) and warmed to room temperature for 4 hours. After this time the reaction was cooled to O0C and carefully treated with 2M HCI(aq) and stirred for 20 minutes. The reaction was filtered through a pad of celite and the pad was washed with diethyl ether. The collected solution was partitioned between brine and diethyl ether. The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo to give an oil. This was purified by flash chromatography to give (1- fluoromethyl-cyclohexyl) methanol, 4, as a colourless oil (67%).(1 -Fluoromethyl-cyclohexyl) methanol, 4, was dissolved in anhydrous DCM under N2 and cooled to -2O0C. NEt3 (1.1eq) was added and the reaction was stirred for 5 minutes. This was then treated dropwise with triflic anhydride (1 1eq) and the solution was stirred at O0C for 1hour. The reaction mixture was poured onto ice and the organics were washed with 1M HCI (aq), saturated NaHCO3 (aq) and brine, then dried over MgSO4, filtered and concentrated in vacuo, to give trifluoro-methanesulfonic acid-1-fluoromethyl-cyclohexylmethyl ester, 5, as an amber oil which was used immediately without further purification in the next step.N-(Diphenylmethylene)glycine ethyl ester was dissolved in DMF and under a nitrogen atmosphere was cooled to O0C. This was treated with KO’Bu (1.1eq) and stirred for 20 minutes. To this solution was added trifluoro-methanesulfonic acid-1-fluoromethyl-cyclohexylmethyl ester, 5 dropwise. The reaction mixture was stirred at room temperature under nitrogen overnight then poured into a 1 :1 mixture of diethyl ether : NH4CI (aq). The phases were separated and the aqueous phase was washed twice with diethyl ether. The organic phases were combined and washed several times with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purified by flash column chromatography to give 2-(benzhydrylidene- amino)-3-(1 fluoromethyl-cyclohexyl) propionic acid ethyl ester, 6 (28%).2- (Benzhydrylidene-amino)-3-(1-fluoromethyl-cyclohexyl)propionic acid ethyl ester, 6, was taken up in 1,4-dioxan and treated with 2 M NaOH (aq) (2eq) with stirring. After the starting EPO material had been consumed (tic), the reaction mixture was acidified by addition of 2M HCI (aq) and stirred overnight at room temperature. The solution was concentrated in vacuo and the residue was partitioned between TBME and water. The pH of the aqueous phase was adjusted to p H 7 by careful addition of 2M NaOH (aq) prior to lyophilisation. The resulting residue was then suspended in 10% Na2CO3 (aq) and dioxan until a homogeneous solution was obtained. Fmoc chloride was added portion wise to the ice-cooled solution over 12 hrs and this was allowed to stir at room temperature overnight. The reaction mixture was washed with TBME and the resulting aqueous was acidified with 2M HCI (aq) and allowed to freeze dry. The resulting solid was triturated with methanol and the mother liquors were collected by filtration and concentrated in vacuo. To remove last traces of salts the resulting solids were partitioned between water and ethyl acetate. The organics were dried over MgSO4, filtered and concentrated in vacuo to give 2-(9H-fluoren-9-ylmethoxycarbonylamino)-…
The synthetic route of 1139-13-5 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; MEDIVIR UK Ltd; PEPTIMMUNE, Inc; WO2006/64286; (2006); A1;,
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