Tetrahydrofuran → (r,r)-Di-sec-butylphenol

To a 100-ml three-necked flask equipped with a magnetic stirrer, a reflux condenser, a thermocouple and an N2 inlet, was added tetrahydrofuran (THF) (9 ml), (R,R,R)-1-phenylethylcarbamic acid-2,6-di-sec-butylphenyl ester (1 g, 2.8 mmol), and 1.0 M sodium hydroxide (11.4 ml, 11.4 mmol). The resulting clear mixture was heated under N2 at 55-60° C. using a heating mantle and continued to stir at this temperature while monitoring the progress of the reaction by HPLC. After the reaction was finished (6-8 h) as judged by HPLC, the reaction mixture was cooled to 15° C. and filtered to remove precipitated urea. The filtered cake was washed with cold THF (5 ml). The filtrate and the wash were combined, acidified to pH 2-3 with 3.0 M hydrochloric acid (HCl) (3.5 ml). After stirring for 10 minutes (min), ether (10 ml) was added and then resulting mixture was vigorously stirred for 15 min after which layers were separated. The organic layer was washed with 3.0 M HCl (3 ml), brine (5 ml), dried magnesium sulfate (MgSO4), filtered to remove the drying agent, and then concentrated on a rotavap to give a semi solid yellow residue which was stirred with methyl tertiary butyl ether (MTBE) (3 ml) for 15 min and then filtered. The filtered cake was washed with MTBE (2 ml). The filtrate and the wash were combined, and then concentrated on a rotavap to give the title compound as a yellow oil (0.6 g, 100% crude yield) that was found to be greater than 93 A % pure by HPLC. The 1H NMR (DMSO-d6) was found to be consistent with the structure.

1. customTo a 100-ml three-necked flask equipped with a magnetic stirrer, a reflux condenser
2. customthe progress of the reaction by HPLC
3. custom(6-8 h)
4. temperaturethe reaction mixture was cooled to 15° C.
5. filtrationfiltered
6. customto remove
7. customprecipitated urea
8. washThe filtered cake was washed with cold THF (5 ml)
9. stirringAfter stirring for 10 minutes (min), ether (10 ml)
10. additionwas added
11. customresulting mixture
12. stirringwas vigorously stirred for 15 min after which layers
13. customwere separated
14. washThe organic layer was washed with 3.0 M HCl (3 ml), brine (5 ml), dried magnesium sulfate (MgSO4)
15. filtrationfiltered
16. customto remove the drying agent
17. concentrationconcentrated on a rotavap
18. customto give a semi solid yellow residue which
19. filtrationfiltered
20. washThe filtered cake was washed with MTBE (2 ml)
21. concentrationconcentrated on a rotavap

ORD-Eintrag

ord-8dd0dcb492c4403289dfa51c4ae4628f

Quelldatensatz

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08871815B2