Synthesis
1. Sodium tert-butoxide (662 mg, 6.47 mmol) was suspended in DMF (20 mL) at 0 °C.
2. 4-nitrophenylacetonitrile (1000 mg, 6.18 mmol) was added to the above suspension and the reaction was stirred for 10 min.
3. Iodomethane (400 μL, 6.47 mmol) was added dropwise over 15 min, keeping the reaction temperature at 0-10 °C. 4.
4. The reaction mixture was stirred at 0-10 °C for 15 min, then brought to room temperature and continued stirring for 15 min.
5. Sodium tert-butoxide (662 mg, 6.47 mmol) was added again and the reaction was stirred for 15 minutes.
6. Iodomethane (400 μL, 6.47 mmol) was added dropwise over 15 minutes and the reaction mixture was stirred overnight.
7. Sodium tert-butoxide (192 mg, 1.94 mmol) was added and the reaction was stirred at 0 °C for 10 min.
8. iodomethane (186 μL, 2.98 mmol) was added and the reaction was stirred for 1 hour.
9. The reaction mixture was partitioned with 1N HCl (50 mL) and ethyl acetate (75 mL).
10. The organic layer was washed sequentially with 1N HCl and saturated saline, dried over anhydrous sodium sulfate and concentrated.
11. 2-Methyl-2-(4-nitrophenyl)propionitrile was obtained as a green waxy solid (1.25 g, 99% yield). 12. The product was analyzed by 1H NMR.
12. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 8.9 Hz, 2H), 7.66 (d, J = 8.9 Hz, 2H), 1.77 (s, 6H).
References
[1] Patent: US2015/231142, 2015, A1. Location in patent: Paragraph 0720
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 17, p. 2203 - 2214
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 11, p. 4834 - 4848
[4] Patent: WO2018/208132, 2018, A1. Location in patent: Paragraph 321-325
[5] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 24, p. 7585 - 7596
