((R)-4,4-dimethylpyrrolidin-2-yl)methanol

493035-98-6

1610034-33-7

Step 4: Synthesis was carried out with reference to the method described in US Patent US20070032433 A1. To a solution of (R)-5-(hydroxymethyl)-3,3-dimethylpyrrolidin-2-one (2.91 g, 20.30 mmol) in tetrahydrofuran (THF, 50.8 mL) was slowly added lithium aluminum hydride (2.0 M THF solution, 12.18 mL, 24.36 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 16 hours. Subsequently, lithium aluminum hydride (2.0 M THF solution, 12.18 mL, 24.36 mmol) was added again and the reaction solution was heated to reflux for 6 hours. After cooling, lithium aluminum hydride (2.0 M THF solution, 12.18 mL, 24.36 mmol) was added a third time and refluxing was continued overnight. Upon completion of the reaction, the mixture was cooled to 0 °C in an ice bath and water (3.67 mL), 15% NaOH aqueous solution (3.67 mL) and water (10.9 mL) were added sequentially. After vigorous stirring for 1 h at room temperature, the filtrate was filtered through a medium porosity sintered glass funnel and the filter cake was padded with cotton and diatomaceous earth and washed with ethyl acetate (EtOAc). The filtrate was concentrated to give the crude product (R)-(4,4-dimethylpyrrolidin-2-yl)methanol (2.29 g, 17.73 mmol, 87% yield) as a yellow viscous oil. The mass spectrum (ESI) showed m/z 130.1 [M + H]+.