Synthesis
Step 2: 2-Cyclobutylacetonitrile (15.00 g, 157.66 mmol, 1.00 eq.) was dissolved in 6 M hydrochloric acid (150 mL, 5.71 eq.) and the reaction was stirred for 16 hours at 120 °C. After completion of the reaction, the mixture was diluted with distilled water (500 mL) and extracted with ethyl acetate (200 mL x 2). The organic phases were combined and washed with distilled water (400 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 2-cyclobutylacetic acid (16.00 g, 140.18 mmol, 88.9% yield) as a colorless liquid. NMR hydrogen spectrum (CDCl3, 400MHz) δ: 2.69-2.68 (m, 1H), 2.47-2.45 (m, 2H), 2.17-2.15 (m, 2H), 1.89-1.87 (m, 2H), 1.75-1.70 (m, 2H).
References
[1] Patent: WO2017/21969, 2017, A1. Location in patent: Page/Page column 62; 54
[2] Journal of medicinal chemistry, 1963, vol. 6, p. 221 - 227
[3] Molecular Crystals and Liquid Crystals (1969-1991), 1989, vol. 168, p. 229 - 246
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 18, p. 4715 - 4722
[5] Journal of the American Chemical Society, 1994, vol. 116, # 19, p. 8843 - 8844
