Diethyl Ether → 1-Phenylethanol, (R)-

Temperature

-5 °C

Anhydrous zinc bromide (11.37 g) was charged to a dry, stirred 250 ml flask filled with nitrogen. Dried diethylether (75 ml) was added and the slurry heated to reflux until a homogenous solution. A 3molar ethereal solution of phenylmagnesium bromide (33.3 ml) was slowly added. Solvent was distilled from the reaction mixture at ambient pressure, whilst maintaining a constant volume by addition of toluene until a distillate temperature of 110° C. was reached. The hot slurry was screened under a nitrogen atmosphere using an in-line sintered glass filter. The filtrates were received into a dry, stirred 250 ml flask and cooled to −5° C. D(+) diethyinorephedrine (0.64 g) was added and the acetaldehyde (2.2 g) in toluene (5 ml) charged from a dropping funnel. The reaction mixture was warmed to ambient temperature, stirred for a total of 12 hours, then cooled on an ice bath and quenched by addition of dilute hydrochloric acid. The organic layer was separated, washed with an equal volume of water and concentrated to yield a crude product (4.62 g). This was further purified by chromatography to give 3.86 g (R)phenylethanol of 17% ee, measured by chiral GC. The product was identified by gas chromatographic comparison with authenticated material.

1. additionfilled with nitrogen
2. temperaturethe slurry heated
3. temperatureto reflux until a homogenous solution
4. distillationSolvent was distilled from the reaction mixture at ambient pressure
5. temperaturewhilst maintaining a constant volume
6. additionby addition of toluene until a distillate temperature of 110° C.
7. filtrationfilter
8. stirringstirred 250 ml flask
9. additionD(+) diethyinorephedrine (0.64 g) was added
10. additionthe acetaldehyde (2.2 g) in toluene (5 ml) charged from a dropping funnel
11. temperatureThe reaction mixture was warmed to ambient temperature
12. stirringstirred for a total of 12 hours
13. temperaturecooled on an ice bath
14. customquenched by addition of dilute hydrochloric acid
15. customThe organic layer was separated
16. washwashed with an equal volume of water
17. concentrationconcentrated
18. customto yield a crude product (4.62 g)
19. customThis was further purified by chromatography

ORD record

ord-4807d43b9e54492a99d86f15ece45394

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06258967B1