N,N-Dimethylcyclopropanecarboxamide → Cyclopropyl[4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenyl]methanone

Temperature

-78 °C

A solution of 4-bromo-α,α-dimethyl-α-(4,4-dimethyloxazolin-2-yl)toluene, prepared according to Example 2, (10.0 g. 0.0338 mole) in 400 mL THF was cooled to −78° C., n-butyllithium (16 mL, 0.042 mole) was added via syringe, and the mixture was stirred at −78° C. for 30 minutes. While keeping the temperature below −75° C., N,N-dimethyl cyclopropylcarboxylic acid amide (11.5 g, 0.102 mole) in 30 mL THF was added dropwise, and the mixture was stirred at −78° C. for 30 minutes. The mixture was allowed to warm to −15° C., and was quenched with water. The product was extracted with methylene chloride, washed with saturated NaCl solution, dried over Na2SO4, and concentrated. The residue was cooled to 0° C., treated with minimal acetonitrile, and filtered, to afford 6.95 g of 4-(cyclopropyl-oxo-methyl)-α,α-dimethyl-α-(4,4-dimethyloxazolin-2-yl)toluene as a white solid (72%).

1. additionwas added dropwise
2. stirringthe mixture was stirred at −78° C. for 30 minutes
3. temperatureto warm to −15° C.
4. customwas quenched with water
5. extractionThe product was extracted with methylene chloride
6. washwashed with saturated NaCl solution
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. temperatureThe residue was cooled to 0° C.
10. additiontreated with minimal acetonitrile
11. filtrationfiltered

ORD record

ord-777c80c668ed4281abd7e165b30cedb2

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08476445B2