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. 456-64-4, name is 1,1,1-Trifluoro-N-phenylmethanesulfonamide, A new synthetic method of this compound is introduced below., Formula: C7H6F3NO2S
Dissolve 2,6-dimethoxynaphthalene 37.6 g (0.20 mol) and 4-(2-(piperidin-1- yl) ethoxy) benzoyl chloride 64.0 g (0.21 mol) in 800 mL of dichloromethane. Add aluminum chloride 133 g (1.00 mol) portionwise and slowly (the first 30 to 50 g must be added slowly to keep the acylation reaction under control so the solvent does not boil off). After all the aluminum chloride has been added, stir the reaction until no more undemethylated compound can be detected either by TLC or HPLC (about 5 hours). Slowly pour the reaction mixture into 1 L of ice/water with vigorous stirring. Decant the top layer water into a separation funnel. Wash the dichloromethane solution and the precipitate with 2N HCl and decant the aqueous layer again into the separation funnel. Extract the aqueous layer with dichloromethane. Adjust the combined dichloromethane solution and the precipitate pH to 8 first with IN NaOH then with saturated NaHCO3. Filter the mixture. Slurry the solid repeatedly with dichloromethane. Separate the layers of the filtrate and extract the aqueous phase with dichloromethane. Wash the combined organic with brine and dry over MgS04. Treat the dichloromethane solution with charcoal and filter through a prepackaged”suppelco”silica gel funnel. Evaporate the solvent to give 61.2 g (75.5%) of 6-methoxy-1- [4- (2-piperidin-1-yl-ethoxy)-benzoyl]- naphthalen-2-ol. Couple 6-methoxy-1- [4- (2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-ol and 2,4-dibenzyloxyphenyl boronic acid to provide 2- (2, 4-dibenzyloxyphenyl)-6-methoxy-l- [4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalene by the procedure analogous to that described above in the procedure for 5- {6-benzyloxy-1- [4- (2-piperidin-1-yl-ethoxy)- phenoxy]-naphthalen-2-yl}-2-methyl-isoindole-1, 3-dione. Dissolve 10.5 g (20.0 mmol) 2- (2, 4-dibenzyloxyphenyl)-6-methoxy-l- [4- (2- piperidin-1-yl-ethoxy)-benzoyl]-naphthalene in 150 mL of THF. Add LAH 1.5 g (37.0 mmol) portionwise with vigorous stirring at 0 C. After the addition, allow the reaction to warm up to room temperature and then stir for 3 hours. Cool the reaction in an ice bath and slowly quench with saturated Na2SO4. Filter off the solid A1203 and wash the filter cake with THF (2x50mL). Combine the filtrates, concentrate and purify the residue by flash chromatography on silica gel using CH2Cl2 : MeOH (9: 1) as eluent to afford 2- methoxy-5- {hydroxy- [4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-6-(2, 4- benzyloxyphenyl)-naphthalene. Heat 2-methoxy-5- {hydroxy- [4- (2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-6- (2, 4- benzyloxyphenyl) -naphthalene to 60C in THF containg 10% (by weight) of Pd/C (30%) catalyst, overnight under 50 psi of hydrogen atmosphere to afford 2-methoxy-5- {hydroxy- [4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-6-(2-hydroxy-4-benzyloxyphenyl)- naphthalene. Treat the THF solution of 2-methoxy-5- {hydroxy- [4- (2-piperidin-1-yl- ethoxy)-phenyl]-methyl}-6- (2-hydroxy-4-benzyloxyphenyl)-naphthalene with 10% (by mol) of concentrated HCl to give I-12- [4- (8-benzyloxy-2-methoxy-5H-6-oxa-chrysen-5- yl)-phenoxy]-ethyl}-piperidine. Dissolve 1- {2- [4- (8-benzyloxy-2-methoxy-5H-6-oxa-chrysen-5-yl)-phenoxy]- ethyl}-piperidine (680 mg) in a mixture of 250 ml ethanol and 150 ml THF with warming. Add a slurry of 300 mf 10 % Pd/C in ethanol and react under 1 atmosphere of hydrogen for 18 hours. Filter the catalyst and evaporate the solvent to yield 465 mg of 2- methoxy-5- [4- (2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-oxa-chrysen-8-ol. Dissolve 2-methoxy-5- [4- (2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-oxa-chrysen-8- ol (118 mg. , 0.245 mmoles) in 20 ml methylene chloride and add N- phenyltrifluoromethanesulfonimide (400 mg, . 1.12 mmoles) followed by 1.0 ml of diisopropylethyl amine and stir for 72 hours. Evaporate the solution to a paste and purify by running through an SCX column in methanol (elute with 2N ammonia/methanol) to give 125 mg of the title compound: 125 mg (83%).
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; ELI LILLY AND COMPANY; WO2005/73205; (2005); A1;,
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