Hydrochloric Acid → 3-(6-[N,N-bis(tert-butoxycarbonyl)amino]-5-methyl-pyridin-3-yl)-2-hydroxymethyl-2-methyl-propionic acid ethyl ester

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Reaction Steps

Methyl chloroformate (338 μL, 4.4 mmol) was added dropwise to a solution of crude 2-(6-[N,N-bis(tert-butoxycarbonyl)amino]-5-methyl-pyridin-3-yl methyl)-2-methyl-malonic acid monoethyl ester (1.9 g) and Et3N (641 μL, 4.6 mmol) in THF (30 mL) at −20° C. The reaction mixture was stirred for 50 min., filtered and added dropwise to a suspension of NaBH4 (182 mg, 4.8 mmol) in THF (30 mL) at −20° C. The reaction was stirred for 16 h at room temperature. 0.5 M HCl was added followed by methylene chloride. The organic phase was washed with brine and dried. Concentration under reduced pressure followed by chromathography (toluene/EtOAc, 10:1→1:3) gave 3-(6-[N,N-bis(tert-butoxycarbonyl)-amino]-5-methyl-pyridin-3-yl)-2-hydroxymethyl-2-methyl-propionic acid ethyl ester (885 mg, 49%).

Provenance & Evidence