Ethyl formate → (2E)-2-(hydroxymethylene)-4,4-dimethylcyclohexanone

Temperature

2.5 °C

4,4-Dimethylcyclohexanone (20 g), ethyl formate (15.8 g, 1.35 eq) and tetrahydrofuran (100 ml) were charged in a 250 ml flask and the mixture was cooled to 0-5° C. Potassium t-butoxide (1M in tetrahydrofuran 191 mL, 1.2 equiv) was slowly added while maintaining the temperature below 0° C. The reaction mixture was mixed at −5 to +5° C. and monitored for completion by GC analysis. After mixing overnight, no starting material was observed. Water (140 mL) was slowly added, and the resulting mixture was extracted with heptane (150 mL). The pH of the aqueous layer was adjusted with 6 M HCl to pH=1-2 (˜40 g HCl) and the extracted with toluene (80 mL). The organic layer was washed with 20% aqueous NaCl (2×140 mL). The product solution in toluene was used directly in the next step within 12 hours (storage at 0° C.).

1. temperaturewhile maintaining the temperature below 0° C
2. additionThe reaction mixture was mixed at −5 to +5° C.
3. additionAfter mixing overnight
4. extractionthe resulting mixture was extracted with heptane (150 mL)
5. extractionthe extracted with toluene (80 mL)
6. washThe organic layer was washed with 20% aqueous NaCl (2×140 mL)
7. custom(storage at 0° C.)

ORD record

ord-aacb6198ecfd42edad815464150fba1f

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168784B2