1-BENZYL-3-(ETHYLAMINO)PYRROLIDINE synthesis

Yield:115445-21-1 95%

Reaction Conditions:

Stage #1: (R)-N-(1-benzylpyrrolidine-3-yl)acetamidewith lithium aluminium tetrahydride in tetrahydrofuran at 20;Heating / reflux;
Stage #2: with sodium hydroxide;water in tetrahydrofuran at 5; for 1 h;

Steps:

I.11

To a mechanically stirred solution of N-[(3R)-1-(phenylmethyl)- 3-pyrrolidinyl]acetamide (157.4 g, 721 mmol) in tetrahydrofuran (THF) (300 ml) at ambient temperature was added lithium aluminum hydride (1.3L, 1.3 mol, 1 M in THF) dropwise over 1.5 hrs. The reaction was heated at reflux for 6 hrs, and then allowed to stir at ambient temperature overnight. The reaction was cooled to 5⁰C and quenched by the very slow addition of water (80 ml_) followed by 15% NaOH (80 ml_) and additional water (240 ml_). This mixture was allowed to stir for 1 hr before filtering. The filter cake was rinsed with THF (2 X 400 ml_), and the filtrate was concentrated. Fresh THF (500 ml_) was added, and the mixture was concentrated again to afford the desired crude product as a yellow oil (140.1 g, 95%): ¹H NMR (400 MHz, CDCI₃) δ ppm 7.18 - 7.32 (m, 5 H), 3.57 (d, J = 1 .64 Hz, 2 H), 3.24 - 3.33 (m, 1 H), 2.72 (dd, J = 9.25, 6.78 Hz, 1 H), 2.45 - 2.63 (m, 3 H), 2.31 (dd, J = 9.35, 5.14 Hz, 1 H), 2.05 - 2.16 (m, 1 H), 1 .53 (dddd, J = 13.06, 7.93, 5.40, 5.27 Hz, 1 H), 1.06 (t, J = 7.14 Hz, 3 H).

References:

WO2009/76387,2009,A1 Location in patent:Page/Page column 23-24