octanal

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3.5 g (15.1 mmol) of trichloroisocyanuric acid, 3.7 g (45.1 mmol) of sodium acetate and 10 mg (0.06 mmol) of TEMPO were suspended in 40 ml of methylene chloride in a 100 ml sulphonation flask and the suspension was cooled to (-7)-(-9)° C. while stirring. A solution of 5 g (38.4 mmol) of 1-octanol in 20 ml of methylene chloride was dosed in within 20 minutes, whereupon the mixture was held at (-7)-(-9)° C. for 80 minutes. Thereafter, the reaction had finished. For the working up, the white precipitate was filtered off and the filtrate was washed with sodium bicarbonate solution and with sodium chloride solution. Distillation of the crude product gave 4.5 g (91%) of octanal, GC content: (98.2%) (area percent). the suspension was cooled to (-7)-(-9)° C was dosed in within 20 minutes, whereupon the mixture For the working up, the white precipitate was filtered off the filtrate was washed with sodium bicarbonate solution and with sodium chloride solution Distillation of the crude product

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At room temperature, a three-necked flask fitted with reflux condenser, internal thermometer, dropping funnel and stirrer was charged, under nitrogen protective gas, with 5.5 g of zinc powder (84 mmol) in 34 ml of ethyl acetate. After 1.6 ml of trimethylchlorosilane (12.5 mmol) had been added, the mixture was heated at 65° C. Following cooling to 60° C., 7.2 g of octanal (56 mmol) were added, and over the course of 4 min, 11.2 g of methyl 2-bromopropionate (67 mmol) were added dropwise, the temperature being maintained at 65° C. by external cooling. The mixture was then stirred at 60° C. for 5 min and, after cooling to 0° C., acidified with 40 ml of 2 N hydrochloric acid to a pH of 1 and stirred for 30 min. Excess zinc was removed by filtration and the organic phase separated. The organic phase was then stirred at 0° C. with 40 ml of 0.5 N hydrochloric acid and finally washed with 20 ml of saturated sodium hydrogen carbonate solution. Following phase separation and drying over sodium sulfate, the solvent was removed by distillation under reduced pressure. Methyl 3-hydroxy-2-methyldecanoate was obtained in a yield of 10.2 g (85% of theory) with a boiling point of 68° C. (0.04 mbar). The diastereomer ratio was 2:1. At room temperature, a three-necked flask fitted with reflux condenser Following cooling to 60° C. the temperature being maintained at 65° C. by external cooling after cooling to 0° C. stirred for 30 min Excess zinc was removed by filtration the organic phase separated The organic phase was then stirred at 0° C. with 40 ml of 0.5 N hydrochloric acid finally washed with 20 ml of saturated sodium hydrogen carbonate solution Following phase separation drying over sodium sulfate the solvent was removed by distillation under reduced pressure

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At room temperature, a three-necked flask fitted with reflux condenser, internal thermometer, dropping funnel and stirrer was charged, under nitrogen protective gas, with 11.1 g of zinc powder (169 mmol) in 70 ml of ethyl acetate. After 3.2 ml of trimethylchlorosilane (25 mmol) had been added, the mixture was heated at 65° C. for 30 min, then left to cool to 60° C., following which, over the course of 6 min, a mixture of 21 g of methyl bromoacetate (137 mmol) and 16 g of octanal (125 mmol) was added dropwise, the temperature being maintained at 65° C. by external cooling. The mixture was then stirred at 55° C. for 5 min, and after cooling to 0° C., was acidified with 75 ml of 2 N hydrochloric acid to a pH of 1 and stirred for 30 min. Excess zinc was removed by filtration and the organic phase separated. The organic phase was then stirred at 0° C. with 80 ml of 1 N hydrochloric acid, and finally washed with 80 ml of saturated sodium hydrogen carbonate solution. Following phase separation, the solvent was removed by distillation under reduced pressure. For the ester hydrolysis, the crude product was treated with a solution of 15.4 g of potassium hydroxide (232 mmol) in 140 ml of water and stirred for 40 min at 50° C., during which a clear solution formed. The solution was extracted with 2×20 ml of toluene, and the aqueous phase was acidified at 0° C. with 100 ml of 2 N hydrochloric acid to a pH of 1 and extracted with 3×20 ml of ethyl acetate. The organic extracts were dried over sodium sulfate and the solvent was removed by distillation under reduced pressure. 3-Hydroxydecanoic acid was obtained in a yield of 21 g (89% of theory). The compound has a melting point of 58° C. following recrystallization from petroleum ether. At room temperature, a three-necked flask fitted with reflux condenser left to cool to 60° C. was added dropwise the temperature being maintained at 65° C. by external cooling after cooling to 0° C. stirred for 30 min Excess zinc was removed by filtration the organic phase separated The organic phase was then stirred at 0° C. with 80 ml of 1 N hydrochloric acid finally washed with 80 ml of saturated sodium hydrogen carbonate solution Following phase separation the solvent was removed by distillation under reduced pressure For the ester hydrolysis stirred for 40 min at 50° C., during which a clear solution formed The solution was extracted with 2×20 ml of toluene was acidified at 0° C. with 100 ml of 2 N hydrochloric acid to a pH of 1 extracted with 3×20 ml of ethyl acetate The organic extracts were dried over sodium sulfate the solvent was removed by distillation under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: At room temperature, a three-neck flask equipped with a reflux condenser, internal thermometer, dropping funnel and stirrer under nitrogen protective gas was initially charged with 7.1 g of zinc powder (108 mmol) in 42 ml of ethyl acetate. After 1.7 ml of trimethylchlorosilane (13.4 mmol) had been added, the mixture was heated to 60° C. for 15 min, then allowed to cool to 55° C. and 15.3 g of undiluted methyl bromoacetate (100 mmol) were subsequently added dropwise within 7 min, and the temperature was maintained at 65° C. by external cooling. The mixture was then stirred at 50° C. for 15 min. After cooling to 0° C., 10.7 g of undiluted octanal (83 mmol) were added, and the temperature was maintained at 5° C. by external cooling. After stirring had been continued at 50C for 30 min, 25° C. for 2 h and 40° C. for 20 min, the mixture was cooled to 0° C., acidified with 30 ml of 10% hydrochloric acid to a pH of 1 and the mixture was stirred for 10 min. Excess zinc was then filtered off and the organic phase removed. The organic phase was then stirred with 10 ml of concentrated ammonia solution at 0° C. for 10 min. After the phase separation, drying was effected over sodium sulfate and the solvent was distilled off under reduced pressure. Methyl 3-hydroxydecanoate was obtained in a yield of 14.2 g (84% of theory) and had a boiling point of 59° C. (0.04 mbar). At room temperature, a three-neck flask equipped with a reflux condenser to cool to 55° C. the temperature was maintained at 65° C. by external cooling After cooling to 0° C. the temperature was maintained at 5° C. by external cooling After stirring the mixture was cooled to 0° C. the mixture was stirred for 10 min Excess zinc was then filtered off the organic phase removed The organic phase was then stirred with 10 ml of concentrated ammonia solution at 0° C. for 10 min After the phase separation drying the solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The foregoing formula may require a solubilizing agent, e.g., the methyl ester of dihydroabietic acid (commercial name: HERCOLYN D® , benzyl benzoate, isopropyl myristate and/or C12 -C14 isoparaffin hydrocarbons.

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture containing 147 mmol of D-tryptophan, 294 ml of 1 N sulfuric acid, 300 ml of ethanol and 294 mmol of octanal is stirred at 45° C. for 72 hours. The solution is concentrated and the residue is taken up in a water/methanol/ammonium hydroxide mixture. The methanol is evaporated at 45° C. and the precipitate is filtered off, washed with water and dried. The solid obtained is solubilized at high temperature in methanol. After cooling, the compound of preparation F crystallizes. It is then filtered and dried. The solution is concentrated The methanol is evaporated at 45° C. the precipitate is filtered off washed with water dried The solid obtained After cooling the compound of preparation F crystallizes It is then filtered dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1.61 g (5.0 mmol) of 3-[4-(imidazo[1,2-a]pyridin-5-ylthio)butyl]thiazolidine-2,4-dione and 0.641 g (5.0 mmol) of 1-octanal in 20 ml of ethanol, 0.05 ml (0.5 mmol) of piperidine was added, followed by refluxing for 1.5 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in dichloromethane, washed with water and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=4/1) to yield 1.54 g (71.4%, yellow oily substance) of the desired product. by refluxing for 1.5 hours After the reaction mixture was cooled the solvent was distilled off The residue was dissolved in dichloromethane washed with water dried after which the solvent was distilled off The residue was purified by column chromatography (eluent, n-hexane/ethyl acetate=4/1)