Sodium hydride → (4S)-4-[2-(4-methoxyphenoxy)ethyl]-2,2-dimethyl-1,3-dioxolane

Temperature

0 °C

To a solution of 2-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanol (Aldrich, 5 g, 34.2 mmol) in THF was added sodium hydride 60% (1.504 g, 37.6 mmol, 1.1 eq) portionwise and the mixture stirred for 1 h (cloudy solution). The mixture was cooled to 0° C. and to it was added 4-methoxybenzyl chloride (5.89 g, 37.6 mmol, 1.1 equivalent (eq.)) in one portion and the mixture stirred at the temperature for 30 min and heated to 65-70° C. overnight. After cooling to rt and quenching with saturated NH4Cl/water, the mixture was extracted with ethyl acetate (2×) and the organic extracts were washed with water, brine and dried over MgSO4. The mixture was filtered and the filtrate was concentrated in vacuo. The crude product was purified by silica gel chromatography (15% ethyl acetate/hexanes) to give desired product as a colorless oil. 1H NMR (400 MHz, Acetone-d6): δ 7.28 (2 H, d), 6.93-6.91 (2 H, m), 4.43 (2 H, s), 4.20-4.14 (1 H, m), 4.04-3.98 (1 H, m), 3.80 (3 H, s), 3.56-3.50 (3 H, m), 1.88-1.76 (2 H, m), 1.31 (3 H, s), 1.28 (3 H, s).

1. stirringthe mixture stirred at the temperature for 30 min
2. temperatureheated to 65-70° C. overnight
3. temperatureAfter cooling to rt
4. customquenching with saturated NH4Cl/water
5. extractionthe mixture was extracted with ethyl acetate (2×)
6. washthe organic extracts were washed with water, brine
7. dry with materialdried over MgSO4
8. filtrationThe mixture was filtered
9. concentrationthe filtrate was concentrated in vacuo
10. customThe crude product was purified by silica gel chromatography (15% ethyl acetate/hexanes)

ORD record

ord-dd3a94d7becb4a148560cbccee21a544

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07238710B2