Cyclohexanol, 3,3-dimethyl- → HCID 58495453, compound

Temperature

-78 °C

Dissolve 3,3-dimethylcyclohexanol (6 g, 47 mmoles) in anhydrous THF (70 mL) under nitrogen atmosphere and cool at −78° C. Add sodium bis(trimethylsilyl)amide (23.4 mL, 47 mmol, 2M solution in THF) to this solution and stir at −78° C. for 30 min before raising to room temperature. Cool down again to −78° C. and add a solution of 2-chloro-5-cyanopyridine (7.1 g, 51.7 mmoles) in anhydrous THF (20 mL) and stir overnight while warming to room temperature. Add saturated aqueous NaHCO3 (100 mL) and extract the aqueous layer with DCM (3×100 mL). Wash the combined organic extracts with brine (200 mL). Dry over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with cyclohexane/EtOAc (1:0 to 9:1 gradient) to afford the desired intermediate as a solid (9.14 g, 84%). MS (ES+) m/z: 231.1 (M+H)+.

1. temperaturebefore raising to room temperature
2. temperatureCool down again to −78° C.
3. temperaturewhile warming to room temperature
4. extractionAdd saturated aqueous NaHCO3 (100 mL) and extract the aqueous layer with DCM (3×100 mL)
5. washWash the combined organic extracts with brine (200 mL)
6. dry with materialDry over MgSO4
7. filtrationfilter
8. concentrationconcentrate in vacuo
9. customPurify the crude mixture by chromatography on silica gel eluting with cyclohexane/EtOAc (1:0 to 9:1 gradient)

ORD record

ord-7e8d7a57d9454887acc99e819d781b9c

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680091B2