3,4-Pyrrolidinedicarboxylic acid, 1-(phenylmethyl)-, 3,4-dimethyl ester, (3S,4S)- synthesis
- Product Name:3,4-Pyrrolidinedicarboxylic acid, 1-(phenylmethyl)-, 3,4-dimethyl ester, (3S,4S)-
- CAS Number:111186-67-5
- Molecular formula:C15H19NO4
- Molecular Weight:277.32
Yield:111186-67-5 83%
Reaction Conditions:
with lithium fluoride in acetonitrile; for 18 h;Sonication;
Steps:
S-27: Dimethyl trans-1-Benzylpyrrolidine-3 , 4- dicarboxylate
A solution of dimethyl fumarate (2.4 g, 16.7 mmol, 1 equiv) and N-benzyl-1-methoxy-N- ((trimethylsilyl)methyl)methanamine (4.8 g, 16.7 mmol, 1 equiv) in 40 mL MeCN was treated with LiE (640 nip, 25 minol, 1.25 equiv) in one portion. The reaction solution was sonicated for 18 hours. The reaction suspension was poured into EtOAc (100 mL) and H20 (150 mL) and the aqueous layer was extracted with EtOAc (2 x 100 mL), washed with saturated aqueous NaCl and dried with Na2SO4. The crude product was purified by flash column chromatography (Si02, 10- 20% EtOAc/hexanes) to provide S-27 as a yellow oil (4.3 g, 83%) . ‘H NMR (400 MHz, CDC13) 7.40 - 7.27 (m, 5H), 3.70 (s, 6H), 3.61 Cs, 2H), 3.51 - 3.40 (m, 2H), 2.96 - 2.85 (m, 2H), 2.84 - 2.72 (m, 2H)
References:
WO2018/5812,2018,A1 Location in patent:Page/Page column 150; 151
