N-methyl-2-pyrrolidone → HCID 59201687, compound

Participants

Reaction Steps

2-(1,3-dioxoisoindolin-2-yl)acetaldehyde (2.04 g, 10.7 mmol) was dissolved into a minimal amount of anhydrous N-methylpyrrolidinone (5.0 mL). Heating was required for full dissolution. The solution was cooled to rt and cyclohexanecarboxaldehyde (5.60 g, 50 mmol) was added. The solution was cooled to 0° C. and solid L-proline (0.40 g, 3.4 mmol) was added in one portion. The reaction was stirred for 1 h at 0° C. and the orange mixture was stored in the refrigerator (6° C.) for 36 h. The crude reaction was taken up in 5:1 Et2O/Hexanes (100 mL) and water (20 mL). The layers were separated and the aqueous phase mixture was extracted with 5:1 Et2O/Hexanes (3×10 mL). The combined organic layers were washed with water (5×10 mL) and brine (3×10 mL), dried over Na2SO4, decanted and stripped to give crude (2S,3S)-3-cyclohexyl-2-(1,3-dioxoisoindolin-2-yl)-3-hydroxypropanal (4.55 g), which was used in the next step without purification.

Provenance & Evidence