Nitrogen → HCID 59536627, compound

Participants

Reaction Conditions

Reaction Steps

Charge a 1 L, 3-neck round bottom flask equipped with a magnetic stirrer, thermal couple, addition funnel and N2 inlet with crude (R)-1-benzyl-3-((S)-1-hydroxy-3-methylbutyl)pyrrolidin-2-one (38.26 mmoles, assumed) and toluene (100 mL). Cool the slightly heterogeneous stirring solution to 0° C. (salt/ice bath) and add a solution of Vitride™ (Rohm & Haas) (65 wt % in toluene, 24 mL, 86.085 mmoles) and toluene (70 mL) drop wise while maintaining a temperature at or below 5° C. Rinse the addition funnel with toluene (10-20 mL). Stir at room temperature overnight (˜16 hr). Cool the reaction mixture to 0° C. (salt/ice bath) and quenched with saturated Rochell's salt solution (200 mL) followed by MTBE (200 mL). Allow the mixture to warm to room temperature with stirring and then stir at this temperature for 1 hour. Separate the organic and aqueous layers and wash the organic layer with H2O (2×200 mL), then brine (200 mL), and then dry over Na2SO4. Filter and concentrate to give the desired intermediate as a brown oil (9.61 g, 38.85 mmoles, >100% yield). 1H NMR (300 MHz, CDCl3) δ 7.36-7.18 (m, 5H), 3.82-3.72 (m, 1H), 3.58 (dd, 2H, 7.61, 20.51 Hz), 2.87 (td, 1H, J=4.10, 8.79 Hz), 2.79-2.70 (m, 1H), 2.48-2.38 (m, 1H), 2.26-2.04 (m, 2H), 1.98-1.64 (m, 3H), 1.46-1.32 (m, 1H), 1.14-0.98 (m, 1H), 0.92 (d, 3H, J=1.18 Hz), 0.89 (d, 3H, J=1.76 Hz). LC/MS=248.1 (M+1).

Provenance & Evidence