Diisopropylamine → 1-(2-cyclopropylethyl)-1-methyl-3,4-dihydronaphthalen-2(1H)-one

Temperature

-30 °C

To a stirring solution of diisopropylamine (4.81 mL, 34.3 mmol) in 50 mL of tetrahydrofuran cooled to 0° C. in an ice bath was added dropwise 1.6M n-butyl lithium in tetrahydrofuran (21.45 mL, 34.3 mmol) over 30 minutes. The solution was cooled to −30° C. and 1-methyl-2-tetralone (5.0 g, 31.2 mmol) in 10 mL of tetrahydrofuran added. The resulting reaction mixture was placed in an ice bath for 2 hour. Cool the solution to −78° C., and added hexamethylphosphoric triamide 20 mL followed by the dropwise addition of (2-Bromo-ethyl)-cyclopropane (6.97 g, 46.8 mmol). The reaction was stirred at rt for 48 hours. Partition the reaction mixture between ethyl acetate and saturated aqueous NH4Cl, extract the aqueous layer 3 times with ethyl acetate. The combined organic layers were washed sequentially with saturated sodium bicarbonate, brine, and then dried over MgSO4. The product was purified by flash chromatography on SiO2, eluting with a 0-10% diethyl ether/hexane gradient yielding the product (4.488 g, 63% yield). 1H NMR (300 MHz, CDCl3): δ ppm 0.01 (m, 2 H) 0.47 (m, 2 H) 0.67 (m, 1 H) 0.98 (m, 2 H) 1.55 (s, 3 H) 1.95 (td, J=12.78, 4.60 Hz, 1 H) 2.37 (ddd, J=13.60, 12.13, 4.78 Hz, 1 H) 2.80 (m, 2 H) 3.19 (m, 2 H) 7.31 (m, 2 H) 7.44 (m, 2 H). MS (ESI+) m/z=229 (M+H)+.

1. customThe resulting reaction mixture
2. temperatureCool the solution to −78° C.
3. customPartition the reaction mixture between ethyl acetate and saturated aqueous NH4Cl
4. extractionextract the aqueous layer 3 times with ethyl acetate
5. washThe combined organic layers were washed sequentially with saturated sodium bicarbonate, brine
6. dry with materialdried over MgSO4
7. customThe product was purified by flash chromatography on SiO2
8. washeluting with a 0-10% diethyl ether/hexane

ORD record

ord-341b90acb3ce43f98388b16a2c236812

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07378414B2