(2S)-1-bromo-2-methylbutane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium (57.5 g, 2.5 mols) was added to ethanol (1 l) to prepare sodium methoxide, followed by adding (S)-2-methylbutyl bromide (317 g, 2.1 mols) and diethyl malonate 400 g, 2.5 mols), refluxing the mixture for 5 hours and distilling off ethanol to obtain oily diethyl (S)-2-methylbutylmalonate. refluxing the mixture for 5 hours distilling off ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 40 g of (S)-4,6-dichloro-2-(p-heptyloxyphenyl)-5-(2-methylbutyl)-pyrimidine [obtainable by reacting (S)-2-methylbutyl bromide with diethyl malonate in the presence of sodium methanolate, followed by condensation of the resultant diethyl (S)-2-methylbutyl malonate with p-heptyloxybenzamidine hydrochloride, and reacting the resultant (S)-4,6-dihydroxy-2-(p-heptyloxyphenyl)-5-(2-methylbutyl)-pyrimidine with phosphoroxy trichloride and dimethylaniline], 400 ml of methanol, 40 ml of triethylamine and 20 g of Pd-C (5%) is hydrogenated at room temperature under normal pressure until the theoretical amount of hydrogen has been taken up. After filtering off the catalyst and distilling off the solvent, the residue is recrystallized from ethanol. (S)-2-(p-Heptyloxyphenyl)-5-(2-methylbutyl)-pyrimidine is obtained. After filtering off the catalyst distilling off the solvent the residue is recrystallized from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 40 g of (S)-4,6-dichloro-2-(p-heptyloxyphenyl)-5-(2-methylbutyl)-pyrimidine [obtainable by reacting (S)-2-methylbutyl bromide with diethyl malonate in the presence of sodium methanolate, followed by condensation of the resultant diethyl (S)-2-methylbutyl malonate with p-heptyloxybenzamidine hydrochloride, and reacting the resultant (S)-4,6-dihydroxy-2-(p-heptyloxyphenyl)-5-(2-methylbutyl)-pyrimidine with phosphoroxy trichloride and dimethylaniline], 400 ml of methanol, 40 ml of triethylamine and 20 g of Pd-C (5%) is hydrogenated at room temperature under normal pressure until the theoretical amount of hydrogen has been taken up. After filtering off the catalyst and distilling off the solvent, the residue is recrystallized from ethanol. (S)-2-(p-Heptyloxyphenyl)-5-(2-methylbutyl)-pyrimidine is obtained. After filtering off the catalyst distilling off the solvent the residue is recrystallized from ethanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Ethynyl-2-(2-(S)-methylbutyl)naphthalene was prepared in a similar manner to 1-ethynyl-2-hexylnaphthalene, except that bromohexane was replaced by 1-bromo-2-(S)-methylbutane.

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution (10 ml) of ethyl 1-(3-cyano-4-hydroxyphenyl)pyrazole-4-carboxylate (1.5 g) in dimethylformamide were added potassium carbonate (0.91 g) and (S)-(+)-1-bromo-2-methylbutane (1 g) with stirring, and the mixture was heated at 90° C. for 2 hours. After the completion of the reaction, the reaction mixture was poured into water and the mixture was acted with ethyl acetate, washed with water and dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was recrystallized from isopropyl ether to give 1.7 g of ethyl 1-(3-cyano-4-((S)-2-methylbutoxy)phenyl)pyrazole-4-carboxylate, melting point 105-106° C. After the completion of the reaction washed with water dried over magnesium sulfate The solvent was evaporated under reduced pressure the obtained residue was recrystallized from isopropyl ether

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Anhydrous tetrahydrofuran (125 mL) was put into a reactor with magnesium (5.7 g, 0.24 mol) and molecular sieves 4A which had been dehydrated and deaerated, followed by charging of argon gas. A small amount of iodine was slowly added to the mixture. (S)-(+)-1-bromo-2-methylbutane (30 g, 0.20 mol) was added dropwise to the slowly stirred mixture so that the reaction mixture was gradually refluxed. After the reaction was complete, the obtained Grignard reagent was transferred to a dropping funnel. The Grignard reagent was added dropwise to a solution being stirred containing phenyltrichlorosilane (50 g, 0.24 mol) in anhydrous tetrahydrofuran (50 mL) in another reactor which had been dehydrated and deaerated, followed by charging of argon gas, at 40° C.-50° C. The reaction mixture was then stirred overnight at room temperature. Hexane (500 mL) was added to the reaction mixture, and the resulting mixture was filtered under pressure, followed by fractional distillation of the filtrate to provide the desired product. was gradually refluxed by charging of argon gas, at 40° C.-50° C The reaction mixture was then stirred overnight at room temperature the resulting mixture was filtered under pressure followed by fractional distillation of the filtrate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Anhydrous tetrahydrofuran (125 mL) was put into a reactor with magnesium (5.7 g, 0.24 mol) and molecular sieves 4A which had been dehydrated and deaerated, followed by charging of argon gas. A small amount of iodine was slowly added to the mixture. (S)-(+)-1-bromo-2-methylbutane (30 g, 0.20 mol) was added dropwise to the slowly stirred mixture so that the reaction mixture was gradually refluxed. After the reaction was complete, the obtained Grignard reagent was transferred to a dropping funnel. The Grignard reagent was added dropwise to a solution being stirred containing phenyltrichlorosilane (50 g, 0.24 mol) in anhydrous tetrahydrofuran (50 mL) in another reactor which had been dehydrated and deaerated, followed by charging of argon gas, at 40° C.-50° C. The reaction mixture was then stirred overnight at room temperature. Hexane (500 mL) was added to the reaction mixture, and the resulting mixture was filtered under pressure, followed by fractional distillation of the filtrate to provide the desired product. was gradually refluxed by charging of argon gas, at 40° C.-50° C The reaction mixture was then stirred overnight at room temperature the resulting mixture was filtered under pressure followed by fractional distillation of the filtrate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Anhydrous tetrahydrofuran (125 mL) was put into a reactor with magnesium (9.5 g, 0.41 mol) and molecular sieves 4A which had been dehydrated and deaerated, followed by charging of argon gas. A small amount of iodine was slowly added to the mixture. (S)-(+)-1-bromo-2-methylbutane (4.5 g, 0.03 mol) was added dropwise to the slowly stirred mixture. In addition, (S)-(+)-1-chloro-2-methylbutane (36 g, 0.34 mol) was added dropwise to the stirred mixture so that the reaction mixture was gradually refluxed. After the reaction was complete, the obtained Grignard reagent was transferred to a dropping funnel. The Grignard reagent was added dropwise to a solution being stirred containing methyltrichlorosilane (80 g, 0.54 mol) in anhydrous diethyl ether (150 mL) in another reactor which had been dehydrated and deaerated, followed by charging of argon gas, at 2° C.-5° C. The reaction mixture was then stirred overnight at room temperature. Hexane (500 mL) was added to the reaction mixture, and the resulting mixture was filtered under pressure, followed by fractional distillation of the filtrate to provide the desired product. was gradually refluxed by charging of argon gas, at 2° C.-5° C The reaction mixture was then stirred overnight at room temperature the resulting mixture was filtered under pressure followed by fractional distillation of the filtrate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction mixture of hydroquinone (18.2 grams); (S)-(+)-1-bromo-2-methylbutane (4.55 grams); anhydrous potassium carbonate (23 grams); and acetonitrile (250 mls.) was allowed to reflux for 40 hours. Flash chromatography using dichloromethane eluant yielded 2.6 grams (48%) of white crystals exhibiting a Fisher-Johns melting point of 44°-45° C. and having the structure ##STR24## confirmed by TLC, NMR, IR and mass spectral analyses. to reflux for 40 hours

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction mixture of hydroquinone (18.2 grams); (S)-(+)-1-bromo-2-methylbutane (4.55 grams); anhydrous potassium carbonate (23 grams); and acetonitrile (250 mls.) was allowed to reflux for 40 hours. Flash chromatography using dichloromethane eluant yielded 2.6 grams (48%) of white crystals exhibiting a Fisher-Johns melting point of 44°-45° C. and having the structure ##STR24## confirmed by TLC, NMR, IR and mass spectral analyses. to reflux for 40 hours

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: [(R)-2-Hydroxy-1-(4-hydroxy-phenyl)-ethyl]-carbamic acid t-butyl ester (10 mmol), (S)-2-methylbutyl bromide (2.60 g, 17 mmol) and Cs2CO3 (7.47 g, 23 mmol) were combined in DMF (50 ml). The reaction mixture was heated at 70° C. overnight. Saturated NH4Cl was added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with brine, then dried over MgSO4, filtered and concentrated to give a white crude solid. The crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes) to afford the title compound (2.09 g, 65% yield of 3 steps) as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.22 (d, J=8.6 Hz, 2H), 6.90 (m, 2H), 5.13 (d, J=6.6 Hz, 1H), 4.73 (br. s., 1H), 3.83 (m, 3H), 3.74 (m, 1 H), 2.39 (br. s., 1H), 1.87 (m, 1H), 1.58 (m, 1H), 1.42 (m, 9H), 1.29 (m, 1H), 1.01 (m, 3H), 0.96 (m, 3H); LCMS (ESI) m/e 324.2 [(M+H), calcd for C18H30NO4 324.4]. to quench the reaction The aqueous layer was extracted with ethyl acetate (3×20 ml) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated to give a white crude solid The crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium (57.5 g, 2.5 mols) was added to ethanol (1 l) to prepare sodium methoxide, followed by adding (S)-2-methylbutyl bromide (317 g, 2.1 mols) and diethyl malonate 400 g, 2.5 mols), refluxing the mixture for 5 hours and distilling off ethanol to obtain oily diethyl (S)-2-methylbutylmalonate. refluxing the mixture for 5 hours distilling off ethanol