3-Hexanol, 1-(phenylmethoxy)- synthesis

Yield:140654-19-9 97%

Reaction Conditions:

Stage #1: ethylmagnesium bromidewith copper(l) iodide in tetrahydrofuran at 0; for 0.5 h;
Stage #2: 2-(2-(benzyloxy)ethyl)oxirane in tetrahydrofuran at 0 - 25; for 1 h;

Steps:

B Step B: (R or S ) -1- (benzyloxy) hexan-3-ol

Set up a reactor R-1 with an agitator. (Note: the reactor R-1: 1 L bottle) , Charged EtMgBr (150 mL, 3.75 X by volume) into reactor R-1. Charged THF (240 mL, 6.00 X by volume) into reactor R-1. Charged CuI (0.85 g, 0.02 X by weight) into reactor R-1 at 0 oC. Stired the mixture at 0 for 0.5 h. Charged (R or S) -2- (2- (benzyloxy) ethyl) oxirane (40.0 g, 1.00 X by weight) into reactor R-1. Stired the mixture at 25 for 1 h. TLC (petroleum ether/ethyl acetate =3/1, R_f= 0.35) showed the reaction was completed. Added aq. NH₄Cl (200 mL, 5.00 X by volume) to the mixture. Extracted the mixture with EtOAc (200 mL x 2, 10.0 X by volume) . Combined the organic layer and washed the organic layer with brine. Dried the organic layer with Na₂SO₄. Concentrated the organic layer to get the crude product. The residue was purified by column chromatography (SiO₂, petroleum ether/ethyl acetate = 50/1 to 5/1) . Target (22.7 g, 47.1%yield, 97.0%purity) as a yellow oil .¹HNMR: 400 MHz CDCl_3:δ 7.30 -7.38 (m, 5H) , 4.54 (s, 2H) , 3.74 -3.83 (m, 1H) , 3.69 -3.73 (m, 1H) , 3.65 -3.67 (m, 1H) , 2.87 (s, 1H) , 1.75 -1.77 (m, 2H) , 1.36 -1.48 (m, 4H) , 0.92 -0.95 (m, 3H) ppm.

References:

WO2020/160711,2020,A1 Location in patent:Paragraph 0847-0848