4-Methylmorpholine → HCID 13685960, compound

Participants

Reaction Steps

A solution containing 2.49 g (10 mmol) N-carbobenzoxy-L-proline and 1.01 g (10 mmol) N-methylmorpholine in approximately 100 ml tetrahydrofuran (THF) was cooled to -20° under nitrogen, and 1.37 g (10 mmol) isobutyl chloroformate was added with magnetic stirring. After five minutes, a solution of 1.17 g (10 mmol) L-leucinol in 5 mL THF was added, and the resulting reaction mixture was stirred for 30 minutes at 0°. THF evaporated under vacuum, and 30 mL water and 100 mL ethyl acetate were added to the resulting residue. After separation of aqueous and organic layers, the organic layer was decanted and retained. The aqueous layer was extracted with a second aliquot (100 mL) of ethyl acetate, and the resulting organic phase was separated. The combined organic layers were washed with 50 mL of ice-cold, 5% aqueous citric acid, followed by 50 mL of an ice-cold, 5% sodium bicarbonate solution. An organic phase was separated, dried over anhydrous magnesium sulfate, and the ethyl acetate was evaporated to provide 3.25 g of crude product. Recrystallization from a mixture of 40 mL ethyl acetate and 25 mL n-hexane gave 2.03 g (5.8 mmol; 58%) of colorless N-carbobenzoxy-L-prolyl-L-leucinol, m.p. 95°-95.5°, α25D-72°, (C=1.03 g/100 mL acetone).

Provenance & Evidence