Cyclohexylisopropylamine → Lithium cyclohexylisopropylamide

Temperature

-78 °C

In a 250 mL round bottomed flask a solution of lithiumisopropylcyclohexylamide was prepared from isopropylcyclohexylamine (6.21 g, 7.23 mL, 44 mmol) in THF (50 mL) and butyllithium (2.5M in hexane, 17.6 mL, 44 mmol). The solution was cooled to -78° C. under nitrogen and N,N-diethyl-3,3-dimethylacrylamide [109] (3.10 g, 20 mmol) in THF (20 mL) was added. After stirring for 30 min at -78° C., the solution was warmed to room temperature and stirred for 5 h. The reaction mixture was then cooled to -78° C., and 1,4-dibromoanisole [112] (5.852 g, 22 mmol) in THF (30 mL) was added via syringe. The solution was stirred at 0° C. for 24 h and then quenched with saturated aqueous ammonium chloride (100 mL) and diluted with ether (30 mL). The organic layer was separated and the aqueous layer was extracted with ether (3×40 mL). The combined organic layers were washed with brine (40 mL), dried with sodium sulfate and concentrated in vacuo to give 4.60 g of crude material. Flash chromatography of the crude material (hexane/ethyl acetate; 9:1) yielded product 113 (1.17 g, 22%) as a light yellow oil.

1. temperaturethe solution was warmed to room temperature
2. stirringstirred for 5 h
3. temperatureThe reaction mixture was then cooled to -78° C.
4. stirringThe solution was stirred at 0° C. for 24 h
5. customquenched with saturated aqueous ammonium chloride (100 mL)
6. additiondiluted with ether (30 mL)
7. customThe organic layer was separated
8. extractionthe aqueous layer was extracted with ether (3×40 mL)
9. washThe combined organic layers were washed with brine (40 mL)
10. dry with materialdried with sodium sulfate
11. concentrationconcentrated in vacuo
12. customto give 4.60 g of crude material

ORD record

ord-fc7f812ab4b24d859d7e1de2f59a1be8

Source dataset

uspto-grants-1996_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05543523