(5S)-5-(Hydroxymethyl)-1-methyl-2-pyrrolidinone → HCID 178481529, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-5-(hydroxymethyl)-1-methylpyrrolidin-2-one (108 mg, 0.84 mmol) (Williams, P. D. et al. Journal of Medicinal Chemistry 1991, 34, 887-900) in 5 mL of THF was added sodium tert-butoxide (100 mg, 1.05 mmol). The mixture was stirred at 22° C. for 20 minutes. The mixture was cooled to 5° C. and a solution of Example 1A (180 mg, 0.42 mmol) in 2 mL of THF was added. The mixture was stirred at 5° C. for 2 hours, then at 22° C. for 1 hour. The solvent was evaporated under reduced pressure. The residue was dissolved in methylene chloride, washed with water, dried over MgSO4 and concentrated. The residue was purified by flash chromatography on SiO2 using an Analogix® Intelliflash280™ (eluted with CH2Cl2:10% MeOH and 3N NH3 in CH2Cl2: 0 to 100%) to afford the title compound; 1H NMR (300 MHz, CDCl3) δ ppm 1.36 (s, 9 H), 1.58-1.73 (m, 1 H), 1.74-2.14 (m, 4 H), 2.14-2.42 (m, 2 H), 2.44-2.64 (m, 1 H), 2.91 (s, 3 H), 3.72-3.91 (m, 2 H), 3.93-4.03 (m, 1H), 4.07 (dd, J=12.0, 4.8 Hz, 1 H), 4.14-4.32 (m, 3 H), 4.39 (dd, J=13.3, 2.6 Hz, 1 H), 6.88 (s, 1 H), 6.99 (d, J=8.7 Hz, 1 H), 7.60 (dd, J=8.7, 2.4 Hz, 1 H), 8.11 (d, J=2.4 Hz, 1 H); MS (ESI) m/z 540 (M+H)+.

Provenance & Evidence