3-amino-1-(thiophen-3-yl)propan-1-ol synthesis

Yield:-

Reaction Conditions:

Stage #1:2-(thiophene-3-carbonyl)acetonitrile with lithium aluminium tetrahydride in tetrahydrofuran at 0 - 65; for 6 h;Inert atmosphere;
Stage #2: with sodium hydroxide in tetrahydrofuran at 0;

Steps:

4.A 3-Amino-1-thiophen-3-yl-propan-1-ol
To a stirred suspension of LAH (1.45 g, 38.1 mmol) in dry THF (120 mL) was added a solution of 3-oxo-3-(thiophen-3-yl)propanenitrile (4.8 g, 31.8 mmol) in dry THF (40 mL) dropwise at 0° C. under nitrogen atmosphere. The mixture was warmed to 25° C. and then heated at 65° C. for 6 hours. After cooling to 0° C., a saturated solution of sodium hydroxide (2 mL) was added dropwise and the mixture was filtered. The filtrate was concentrated to dryness to give crude 3-amino-1-thiophen-3-yl-propan-1-ol which was used in next step without further purification. ¹H NMR (300 MHz, CDCl₃): δ 7.29-7.26 (m, 2H), 7.05 (dd, 1H, J₁=4.8 Hz, J₂=1.2 Hz), 5.04 (dd, 1H, J₁=8.1 Hz, J₂=3.0 Hz), 3.10-3.05 (m, 2H), 1.82-1.77 (m, 2H).

References:

Luk, Kin-Chun US2012/184562, 2012, A1 Location in patent:Page/Page column 14