Synthesis
Step 1: Dissolve (R)-2-(hydroxymethyl)pyrrolidine (2.0 g, 19.8 mmol) in dichloromethane (20 mL) and add 1 M aqueous sodium hydroxide solution (20 mL). A solution of di-tert-butyl dicarbonate (4.32 g, 19.8 mmol) in dichloromethane (10 mL) was added slowly and dropwise at room temperature. The reaction mixture was stirred at room temperature for 5 hours. After completion of the reaction, the organic and aqueous layers were separated. The organic layer was washed twice with distilled water and the aqueous layer was extracted with dichloromethane. All organic layers were combined and dried with anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure to give the crude product. Purification by recrystallization from hexane afforded the intermediate (R)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate in a yield of 2.60 g (65% yield).
References
[1] Patent: US5902819, 1999, A
[2] Patent: WO2006/19833, 2006, A1. Location in patent: Page/Page column 60
[3] European Journal of Organic Chemistry, 2002, # 14, p. 2391 - 2399
[4] Tetrahedron Letters, 1997, vol. 38, # 37, p. 6479 - 6482
[5] Tetrahedron Asymmetry, 1997, vol. 8, # 13, p. 2209 - 2213
