Methanol → 1-Ethyl 2-methyl (2R)-pyrrolidine-1,2-dicarboxylate

To a stirred suspension of D-proline ((R)-29, 13.955 g, 120.0 mmol) and potassium carbonate (K2CO3, 33.17 g, 240.0 mmol, 2.0 equiv) in anhydrous methanol (MeOH, 240 mL, 5925 mmol) at 0° C. was added ethyl chloroformate (28.4 mL, 288 mmol, 2.4 equiv) at room temperature. The resulting reaction mixture was then stirred at room temperature for 18 h. When LCMS showed the reaction was deemed complete, the solvent was removed under reduced pressure. The resulting residue was then treated with water (80 mL) and saturated aqueous NaHCO3 (80 mL) before being extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate (MgSO4), filtered, and concentrated under reduced pressure to give the pure (2R)-1-ethyl 2-methyl pyrrolidine-1,2-dicarboxylate ((R)-30, 18.792 g, 24.14 g theoretical, 77.8% yield) as a colorless volatile oil. For (R)-30: 1H NMR (CDCl3, 400 MHz) δ ppm 4.35 (dd, 0.5H, J=8.7, 3.5 Hz), 4.28 (dd, 0.5H, J=8.7, 3.7 Hz), 4.13 (m, 2H), 3.72 (s, 1.5H), 3.70 (s, 1.5H), 3.59-3.41 (m, 2H), 2.20 (m, 1H), 2.01-1.86 (m, 3H), 1.25 (t, 1.5H, J=7.1 Hz), 1.18 (t, 1.5H, J=7.1 Hz); C9H15NO4(MW, 201.22), LCMS (EI) m/e 201.9 (M++H).

1. customThe resulting reaction mixture
2. customthe solvent was removed under reduced pressure
3. additionThe resulting residue was then treated with water (80 mL) and saturated aqueous NaHCO3 (80 mL)
4. extractionbefore being extracted with EtOAc (2×100 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over magnesium sulfate (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-464c29ff1b424953986897ad766748de

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410265B2