Synthesis
1. cool anhydrous THF (25 mL) under ice bath conditions.
2. a one-time addition of NaH (1.40 g, 35 mmol, 60%) to THF, followed by stirring the mixture at room temperature for 30 minutes and cooling again in an ice bath.
3. a solution of anhydrous THF (6 mL) of 1H-imidazole (2.00 g, 30 mmol) was added slowly and dropwise to the above mixture.
4. The reaction mixture was gradually warmed to room temperature and stirred continuously at this temperature for 1.5 hours.
5. 1-Bromo-3-chloropropane (4.60 g, 30 mmol) was added dropwise to the reaction system, followed by stirring at room temperature overnight.
6. Upon completion of the reaction, MeOH (5 mL) was added all at once to quench the reaction.
7. The reaction mixture was filtered, the filtrate was collected and the solvent was removed by vacuum concentration.
8. The residue was purified using silica gel column chromatography (eluent ratio DCM/MeOH (V/V) = 30:1) to give 1-(3-chloropropyl)-1H-imidazole as a light yellow oil (3.10 g, 73% yield).
References
[1] Tetrahedron Letters, 2010, vol. 51, # 28, p. 3666 - 3669
[2] Patent: WO2014/12360, 2014, A1. Location in patent: Paragraph 00398
[3] Patent: US2015/87639, 2015, A1. Location in patent: Paragraph 0703
[4] Patent: TWI607995, 2017, B. Location in patent: Page/Page column 154
[5] European Journal of Organic Chemistry, 2009, # 19, p. 3249 - 3257
