tert-Butanol → 2,2,6,6-tetramethyltetrahydro-2H-pyran-4-carboxylic acid

Temperature

35 °C

To a solution of 2,2,6,6-tetramethyl-tetrahydro-pyran-4-one (3.00 g, 19.20 mmol), p-toluenesulfonylmethyl isocyanide (4.90 g, 24.96 mmol), and t-butanol (3.06 mL, 32.64 mmol) in 75 mL dimethoxyethane at 0° C. was added potassium t-butoxide (5.38 g, 48.01 mmol) at such a rate that the temperature did not increase above 10° C. After addition was complete the mixture was allow to attain RT and then heated at 35° C. overnight. The mixture was then cooled to RT and 50 mL of diethyl ether was added and the mixture was filtered. The filtrate was concentrated and redissolved in 50 mL of diethyl ether and filtered to remove the ppt. The filtrate was again concentrated and then dissolved in 50 mL of 2.25 M KOH and refluxed overnight. The mixture was cooled and washed with 2×50 mL of DCM. The pH of the aqueous layer was then adjusted to 2 with conc HCl and the product extracted with EtOAc (2×50 mL). The organic phase was dried over Na2SO4, filtered and concentrated to give 2.85 g (80%) of the title compound as an off-white solid which was used without further purification.

1. temperaturedid not increase above 10° C
2. additionAfter addition
3. customto attain RT
4. temperatureThe mixture was then cooled to RT
5. filtrationthe mixture was filtered
6. concentrationThe filtrate was concentrated
7. dissolutionredissolved in 50 mL of diethyl ether
8. filtrationfiltered
9. customto remove the ppt
10. concentrationThe filtrate was again concentrated
11. dissolutiondissolved in 50 mL of 2.25 M KOH
12. temperaturerefluxed overnight
13. temperatureThe mixture was cooled
14. washwashed with 2×50 mL of DCM
15. extractionthe product extracted with EtOAc (2×50 mL)
16. dry with materialThe organic phase was dried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated

ORD record

ord-4e4ed6c1244246dda023519c1e426678

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901314B2