2-[(TETRAHYDRO-2H-PYRAN-4-YL)AMINO]ETHANOL synthesis

Yield:786684-00-2 65.8%

Reaction Conditions:

Stage #1: dihydro-2H-pyran-4(3H)-one;2-hydroxyethylamine in ethanol at 20; for 2 h;
Stage #2: with sodium tetrahydridoborate;ethanol at 20; for 16 h;Cooling with ice;

Steps:

318A 318A.
2-((Tetrahydro-2H-pyran-4-yl)amino)ethanol

A solution of dihydro-2H-pyran-4(3H)-one (5 g, 49.9 mmol) and 2-aminoethanol (3.66 g, 59.9 mmol) in ethanol (50 mL) was stirred for 2 h at RT.
Then the reaction was cooled to ice bath and treated with sodium borohydride (2.83 g, 74.9 mmol) and stirred for 16 h at RT.
The reaction mixture was quenched with saturated aqueous NaHCO₃ solution and extracted with DCM (2*100 mL).
The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 318A (colorless oil, 5.3 g, 32.9 mmol, 65.8% yield).
¹H NMR (300 MHz, DMSO-d₆) δ3.81 (dt, J=11.4, 3.5 Hz, 2H), 3.43 (q, J=5.7 Hz, 2H), 3.29-3.22 (m, 2H), 2.61-2.54 (m, 2H), 1.72-1.70 (m, 2H), 1.26-1.13, 1.08 (d, J=1.1 Hz, 1H), 1.07-1.00 (m, 2H).

References:

US2016/289171,2016,A1 Location in patent:Paragraph 1082