(2R,4R)-1-BOC-2-hydroxyMethyl-4-aMino Pyrrolidine-HCl synthesis

Yield: 92%

Reaction Conditions:

with hydrogen;palladium 10% on activated carbon in methanol at 20; under 775.743 Torr; for 16 h;

Steps:

11
Hydrogenate a mixture of (2R, 4R)-4-azido-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (225 g, 0.93 mol) and 10% palladium on carbon (22.5 g, pre-wetted with toluene) in methanol (2.3 L) at 15 psi of hydrogen at room temperature for 16 h. Filter off the catalyst and concentrate the filtrate to obtain the title compound as an oil (198 g, 92%). ¹H NMR (400 MHz, DMSO-d₆) δ 1.38 (s, 9H), 1.58 (m, IH), 2.16 (m, IH), 2.95 (m, IH), 3.20-3.58 (m, 6H), 3.61 (m, IH), 3.65 (br s, IH).

References:

ELI LILLY AND COMPANY;COATES, David, Andrew;GAVARDINAS, Konstantinos;JADHAV, Prabhakar, Kondaji WO2010/104721, 2010, A1 Location in patent:Page/Page column 25