2,6-Lutidine → 2-(3-(R)-t-Butydimethylsilyloxymethyl-4-(S)-(3-fluorophenyl)pyrrolidin-1-yl)-3-ethylvaleric Acid, 4-methoxybenzyl Ester

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Reaction Steps

A solution of 0.82 g (2.93 mmol) of 3-Ethyl-2-hydroxyvaleric acid, 4-methoxybenzyl ester (step B) in 5 mL of dry CH2Cl2 was cooled in a −78° C. bath and 0.6 mL (3.57 mmol) of trifluoromethanesulfonic anhydride was added. After 5 min, 0.46 mL (4 mmol) of 2,6-lutidine was added and stirred for 15 min. To this solution, 1.3 mL (7.47 mmol) of DIEA was added and after 10 min a solution of 0.907 g (2.93 mmol) of 3-(R)-t-butyldimethylsilyloxymethyl-4-(S)-(3-fluorophenyl)pyrrolidine in 5 mL of CH2Cl2 was added. The cold bath was removed and the reaction was stirred overnight. The reaction was quenched with saturated NaHCO3 and extracted with Et2O. The combined Et2O layer was washed with brine, dried and concentrated. The residue was purified on a flash column using 10% EtOAc-hexane to isolate 1.1 g of the desired product as a mixture of two diastereomers. 1H NMR (CDCl3) 0.06 and 0.16 (6H), 0.87 (m, 15H), 1.2-3.6 (m, 13H), 3.82 (2s, 3H), 5.11 (s, 2H), 6.8-7.4 (m, 8H),

Provenance & Evidence