Hexane → Propanamide, N-[3-(1-hydroxy-4,4-dimethylcyclohexyl)-2-pyridinyl]-2,2-dimethyl-

Temperature

-78 °C

To a solution of N-(pyridin-2-yl)pivalamide (1.1 g, 6 mmol) in tetrahydrofurane (30 mL) was added at −78° C. under nitrogen and stirring a solution of 1.6M n-butyllithium in hexane (7.88 mL, 12.6 mmol). The reaction is exotherm and it turns light yellow. The reaction was stirred for 15 minutes at −78° C. and then for 2 hours at 0° C. The reaction was cooled to −78° C. and 4,4-dimethylcyclohexanone (937 mg, 7.2 mmol) dissolved in tetrahydrofurane (5 mL) was added dropwise. The reaction was warmed to room temperature over night. The reaction was quenched with saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate as the eluent to yield the title compound as a white powder (1.034 g, 57%).

1. waitfor 2 hours at 0° C
2. temperatureThe reaction was cooled to −78° C.
3. additionwas added dropwise
4. temperatureThe reaction was warmed to room temperature over night
5. customThe reaction was quenched with saturated aqueous ammonium chloride solution
6. extractionextracted twice with ethyl acetate
7. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. customthe solvent was evaporated under reduced pressure
11. customThe residue was purified by column chromatography on silica gel

ORD record

ord-e1203f295521454a94f225a36ade1614

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703763B2