* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
(3) A mixture of intermediate 2 (700 g, 2.8 mol, 1.0 eq)Was added to a saturated solution of hydrogen chloride in ethanol (3.0 L)Heating reflux stirring 3h,Stirring was stopped,The ethanol was removed by rotary evaporation,Recrystallization (petroleum ether),To give 580 g of ethyl (1S, 3αR, 6αS) -octahydrocyclopenta [c] pyrrole-1-carboxylate hydrochloride as a white solid. Yield 96.4percent, ee 99.7percent.
Reference:
[1] Patent: CN105601556, 2016, A, . Location in patent: Paragraph 0025; 0045
2
[ 597569-42-1 ]
[ 64-17-5 ]
[ 1147103-42-1 ]
Yield
Reaction Conditions
Operation in experiment
71%
for 2 h; Reflux
The white solid obtained in step (6) was added to 15 L of absolute ethanol, and 2.36 kg of thionyl chloride was added dropwise at room temperature, followed by heating under reflux for 2 hours. After the reaction, the reaction solution was concentrated, The ester was stirred and the precipitated crystals were filtered to give the product 910 g in 71percent yield.
(3) A mixture of intermediate 2 (700 g, 2.8 mol, 1.0 eq)Was added to a saturated solution of hydrogen chloride in ethanol (3.0 L)Heating reflux stirring 3h,Stirring was stopped,The ethanol was removed by rotary evaporation,Recrystallization (petroleum ether),To give 580 g of ethyl (1S, 3alphaR, 6alphaS) -octahydrocyclopenta [c] pyrrole-1-carboxylate hydrochloride as a white solid. Yield 96.4%, ee 99.7%.
The white solid obtained in step (6) was added to 15 L of absolute ethanol, and 2.36 kg of thionyl chloride was added dropwise at room temperature, followed by heating under reflux for 2 hours. After the reaction, the reaction solution was concentrated, The ester was stirred and the precipitated crystals were filtered to give the product 910 g in 71percent yield.
With sodium hydrogencarbonate In 1,4-dioxane; water at 20℃; for 12h;
3.G.1 Synthesis of (1S,3aR,6aS)-2-(tert-butoxycarbonyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid (2)
To a stirred solution of compound 1 (1.1 g, 7.09 mmol) and sodium bicarbonate (1.18 g, 14.1 mmol) in water (20 mL), di-tertiary butyl dicarbonate (2.25 g, 10.6 mmol) in dioxane (20 mL) was added and the reaction mixture was allowed to stir at room temperature for 12 h. After completion of the reaction as indicated by TLC, the reaction mixture was quenched with water and extracted with ethyl acetate. The aqueous layer was acidified by using 1N HCl to pH 2 and extracted with ethyl acetate. The organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a crude residue, which was purified by column chromatography to afford 8 compound 2 (1.3 g, 72%). MS (ESI) m/z 256 [M+1]+