Sodium Hydroxide → 2-Amino-6-ethynylbenzonitrile

Temperature

80 °C

To a solution of 2-amino-6-bromobenzonitrile (1.25 g, 6.34 mmol) and ethynyltrimethylsilane (2.42 g, 12.7 mmol) in dry Et3N (15 mL) was added under N2Cu(I) (60 mg), Pd(PPh3)4 (360 mg) and the mixture was stirred at 80° C. for 20 hours. The reaction mixture was cooled down to room temperature, diluted with ethyl acetate and washed with brine. The organic layer was evaporated and the residue was dissolved in methanol (20 mL), treated with 1M aqueous NaOH solution (1.05 equiv.) and stirred at room temperature for 1 hour. Methanol was evaporated off and the aqueous residue was extracted with CH2Cl2, dried over MgSO4, and purified over silica gel (ethyl acetate/hexanes 75/25) to furnish the desired product in 93% yield as light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 4.54 (s, 1H), 6.24 (br s, 2H), 6.76 (dd, J=0.8, 7.6 Hz, 1H), 6.82 (dd, J=0.8, 8.4 Hz, 1H), 7.28 (dd, J=7.6, 8.4 Hz, 1H). MS 143 (MH+).

1. temperatureThe reaction mixture was cooled down to room temperature
2. washwashed with brine
3. customThe organic layer was evaporated
4. dissolutionthe residue was dissolved in methanol (20 mL)
5. stirringstirred at room temperature for 1 hour
6. customMethanol was evaporated off
7. extractionthe aqueous residue was extracted with CH2Cl2
8. dry with materialdried over MgSO4
9. custompurified over silica gel (ethyl acetate/hexanes 75/25)

ORD record

ord-f76c1ca99e52489c841ac958b2543828

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633186B2