Here is what I've found. First, amine is reacted with acrylates to yield di-ester. Then it is cyclisized to form the Dieckmann product which is decarboxylised using acidic medium. Steps like distilling the di-ester under vacuum can be skipped. The decarboxylation can be done in acetic acid as well.
1-Isopropyl-4-piperidone: Isopropylamine (684 cc.) was dissolved in 1600 cc. of absolute alcohol and to the solution, cooled in an ice-bath, 2800 cc. of ethyl acrylate was added portionwise. The resulting solution was kept for 1week a room temperature and then worked up in the usual manner (6). The di-(beta-carbethoxy-ethyl)-isopropylamine distilled a 128 degrees at 2mmHg.; yield 1600 g.
In a 3-necked, 5-liter, round-bottom flask provided with a Hershberg stirrer, dropping funnel and reflux condenser, 46 g. of sodium was powdered under 1000 cc. of dry toluene. The inside temperature was brought to 90 degrees with an oil-bath, and 518 g. of di-(beta-carbethoxyethyl)isopropylamine was added dropwise with stirring. As the condensation progressed the sodium salt of l-isopropyl-3-carbethoxy-4-piperidoneprecipitated out. When the addition was complete the mixture was heated and stirred at 90 degrees for 3 hours longer. The contents were cooled, 1000 cc. of water added, the toluene was separated, and the aqueous layer was acidified with 480 cc. of concentrated hydrochloric acid. The solution of l-isopropyl-3-carbethoxy-4-piperidone hydrochloride was refluxed until a drop of the solution gave only a faint color with ferric chloride. Most of the water was removed in vacuum and the residue made alkaline with 50% sodium hydroxide solution to about pH 11. The mixture was then extracted with ether. The ether solution was dried over potassium carbonate and the ether removed. The residual oil on fractionation yielded 135 g. of 1-isopropyl-4-piperidone, b p. 103 degrees at 25 mmHg.
Presumably, this will would work with Phenylethylamine too? Sodium suspension is used here to cyclisize the di-ester, but NaOMe/NaOEt Can be used too, although sodium suspension seems to work better with better yields and faster reaction time.
What do you think guys? Will this work with phenylethylamine? I have to intention to try this but maybe someone here will find this helpful.
1-Isopropyl-4-piperidone: Isopropylamine (684 cc.) was dissolved in 1600 cc. of absolute alcohol and to the solution, cooled in an ice-bath, 2800 cc. of ethyl acrylate was added portionwise. The resulting solution was kept for 1week a room temperature and then worked up in the usual manner (6). The di-(beta-carbethoxy-ethyl)-isopropylamine distilled a 128 degrees at 2mmHg.; yield 1600 g.
In a 3-necked, 5-liter, round-bottom flask provided with a Hershberg stirrer, dropping funnel and reflux condenser, 46 g. of sodium was powdered under 1000 cc. of dry toluene. The inside temperature was brought to 90 degrees with an oil-bath, and 518 g. of di-(beta-carbethoxyethyl)isopropylamine was added dropwise with stirring. As the condensation progressed the sodium salt of l-isopropyl-3-carbethoxy-4-piperidoneprecipitated out. When the addition was complete the mixture was heated and stirred at 90 degrees for 3 hours longer. The contents were cooled, 1000 cc. of water added, the toluene was separated, and the aqueous layer was acidified with 480 cc. of concentrated hydrochloric acid. The solution of l-isopropyl-3-carbethoxy-4-piperidone hydrochloride was refluxed until a drop of the solution gave only a faint color with ferric chloride. Most of the water was removed in vacuum and the residue made alkaline with 50% sodium hydroxide solution to about pH 11. The mixture was then extracted with ether. The ether solution was dried over potassium carbonate and the ether removed. The residual oil on fractionation yielded 135 g. of 1-isopropyl-4-piperidone, b p. 103 degrees at 25 mmHg.
Presumably, this will would work with Phenylethylamine too? Sodium suspension is used here to cyclisize the di-ester, but NaOMe/NaOEt Can be used too, although sodium suspension seems to work better with better yields and faster reaction time.
What do you think guys? Will this work with phenylethylamine? I have to intention to try this but maybe someone here will find this helpful.