(3aS,7aS)-6-Phenethyloctahydro-1H-pyrrolo[2,3-c]pyridine hydrochloride synthesis

Yield:912338-15-9 82%

Reaction Conditions:

with hydrogen;palladium(II) hydroxide/carbon in methanol; under 2585.81 Torr; for 16 h;Parr bottle;

Steps:

5; 208.6

Into a 2.5-liter Parr bottle are charged 20% Pd(OH)₂ on carbon (11.2 g, 50% wet) under nitrogen atmosphere. A solution of compound A6 (56 g, 0.15 mol) in methanol (1 L) is added. The mixture is hydrogenated at 50 psi for 16 h until all A6 is consumed. The mixture is filtered through a pad of celite under nitrogen atmosphere. The filtrate is concentrated under vacuum at 35° C. to give an oil. The oil containing A7 and the by-product is dissolved into ethyl acetate. A solution of 6N HCl in IPA (27 mL) is diluted with EtOAc (60 mL) and added to the solution containing A7 over a period of 40 min at 18-27° C. After the addition, the mixture is cooled to 0° C. and stirred for an additional 1 h. Any solid is collected by filtration to obtain A7 hydrochloride salt as a white solid (33 g, 82%): m.p.=172-178° C. ¹H NMR (500 MHz, CDCl₃) δ 7.12-7.32 (m, 5H), 3.50 (s, 1H), 3.15-3.35 (m, 2H), 2.45-2.95 (m, 8H), 2.20 (s, 2H), 1.95 (m, 1H), 1.70 (m, 2H), 1.45 (s, 1H). By treating the hydrochloride salt with aqueous 1N NaOH solution, the free base of A7 is obtained as an oil: ¹H NMR (500 MHz, CDCl₃) δ 7.15-7.35 (m, 5H), 3.05 (m, 1H), 2.96 (q_AB, J=8.2, 4.0 Hz, 1H), 2.87 (m, 2H), 2.70 (m, 2H), 2.60 (m, 1H), 2.49 (m, 2H), 2.40 (bs, 1H), 2.30 (dd, J=11.6, 3.7 Hz, 1H), 2.02 (td, J=11.0, 3.0 Hz, 1H), 1.88 (m, 1H), 1.77 (m, 1H), 1.52 (m, 2H), 1.36 (m, 1H). ¹³C NMR (125 Hz, CDCl₃) δ 141.0, 129.1, 128.7, 126.3, 60.9, 58.6, 55.0, 53.0, 44.9, 36.6, 34.1, 31.9, 27.8. Rotation: α²⁵_Na=-11.5° [c 9.57 mg/1 mL CH₃CN].

References:

US2005/234042,2005,A1 Location in patent:Page/Page column 77-78; 80