Ethyl 1-benzyl-4,4-diMethylpyrrolidine-3-carboxylate synthesis

Yield:261896-28-0 34%

Reaction Conditions:

Stage #1: ethyl 3-methylbut-2-enoate;N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine at 0; for 0.333333 h;Inert atmosphere;
Stage #2: with trifluoroacetic acid in dichloromethane at 0 - 20; for 72 h;Inert atmosphere;

Steps:

Ethyl 1-benzyl-4,4-dimethylpyrrolidine-3-carboxylate (S1e)

To a stirred solution of ethyl 3-methylbut-2-enoate (2.465 g, 19.23 mmol) in toluene (33 mL) was added N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine (6.02 g, 6.49 mL, 23.08 mmol, 91%) at 0 °C under inert atmosphere. After20 min, a solution of TFA (0.219 g, 0.148 mL, 1.923 mmol) in CH2Cl2 (2 mL) was added slowly at 0 °C. Themixture was stirred for 40 min at 0 °C after which the cooling bath was removed and stirring continued for 72 hat rt. The solvent was removed in vacuo to provide a yellow oil that was purified using silica gel chromatographyto provide S1e (1.72, 6.58 mmol, 34% yield) as a colorless oil

References:

Fjelbye, Kasper;Marigo, Mauro;Clausen, Rasmus Pr?torius;Juhl, Karsten [Synlett,2017,vol. 28,# 4,art. no. ST-2016-B0535-L,p. 425 - 428] Location in patent:supporting information