Hydrochloric Acid → (R)-(-)-Methyl mandelate

Temperature

70 °C

To a dispersion of 1.0 g (26.3 mmol) of sodium borohydride in THF (80 ml), there was added 3.95 g (26.3 mmol) of L-(+)-tartaric acid, and the mixture was heated under reflux for four hours in an oil bath at 70° C. with stirring. The resulting mixture was cooled in a cryostat at -20° C., a solution of 1.0 g (6.6 mmol) of phenylglyoxylic acid in THF (5 ml) was added dropwise with stirring over a period of ten minutes, and stirring was continued for 67 hours. The reaction mixture was cooled in an ice bath, 30 ml of 1N HCl was added, and stirring was further continued for 30 minutes. After distilling off the solvent under reduced pressure, the residue was extracted twice with 20 ml ether, and the combined extract was washed with 50 ml of a saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate. The dried solution was concentrated to about 30 ml, and an ethereal solution of diazomethane was added to the concentrate to esterify the reaction product. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography, giving 1.03 g of methyl (R)-(-)-2-hydroxy-2-phenylacetate as a fraction in ethyl acetate:n-hexane (1:5). Its specific rotation [α]D21 was -100.0° (cl. 09, MeOH). The synthesis yield was 93% and the optical yield was 65% e.e. (see Reference 3).

1. temperaturethe mixture was heated
2. temperatureThe resulting mixture was cooled in a cryostat at -20° C.
3. stirringwith stirring over a period of ten minutes
4. stirringstirring
5. temperatureThe reaction mixture was cooled in an ice bath
6. stirringstirring
7. waitwas further continued for 30 minutes
8. distillationAfter distilling off the solvent under reduced pressure
9. extractionthe residue was extracted twice with 20 ml ether
10. extractionthe combined extract
11. washwas washed with 50 ml of a saturated aqueous solution of sodium chloride
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationThe dried solution was concentrated to about 30 ml
14. additionan ethereal solution of diazomethane was added to the
15. concentrationconcentrate
16. distillationAfter distilling off the solvent under reduced pressure
17. customthe residue was purified by silica gel column chromatography

ORD record

ord-b5bef47d23ce4737a8a9452c80f8395d

Source dataset

uspto-grants-1990_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04943652