Reaction #2487458

Reaction equation

N-methoxy-N-methylbenzamide

tert-butyl (4-cyclopropyl-2-methylphenyl)carbamate

sec-butyllithium

→

title compound

Yield 59.5%

tert-Butyl[4-cyclopropyl-2-(2-oxo-2-phenylethyl)phenyl]carbamate

Yield 59.5%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture was stirred at −45° C. for 35 minutes
2. 2
   workup.STIRRINGstirred at room temperature for 2 more hours
3. 3
   OtherThe reaction mixture was quenched with saturated aqueous ammonium chloride solution/water (2/1, 30 mL)
4. 4
   Extractionfollowed by extraction with ethyl acetate
5. 5
   WashThe organic layer was washed with saturated brine
6. 6
   Dryingdried over anhydrous sodium sulfate
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   OtherThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Procedure

Under an argon atmosphere, to a solution of tert-butyl (4-cyclopropyl-2-methylphenyl)carbamate (666 mg) in tetrahydrofuran (13.5 mL) was added dropwise sec-butyllithium (1.08 mol/L hexane-cyclohexane solution, 5.5 mL) at −45° C., and the mixture was stirred for 30 minutes. Next, a solution of N-methoxy-N-methylbenzamide (489 mg) in tetrahydrofuran (1.4 mL) was added dropwise thereto, and the mixture was stirred at −45° C. for 35 minutes and then stirred at room temperature for 2 more hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution/water (2/1, 30 mL), followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (563 mg). 1H-NMR (CDCl3) δ ppm: 0.55-0.70 (2H, m), 0.80-1.00 (2H, m), 1.49 (9H, s), 1.75-1.90 (1H, m), 4.25 (2H, s), 6.85-7.00 (2H, m), 7.20-7.75 (5H, m), 8.00-8.15 (2H, m).

Source