反应详情

温度

0 °C

Under nitrogen, a stirred solution of 10.0 g (36.5 mmol) of N--t--Boc--L--norleucine-N-methoxy-N-methylamide from Step 2 in 100 mL of methylene chloride at 0° C. was treated with 100 mL of trifluoroacetic acid (TFA). The reaction was allowed to warm to ambient temperature and stir. After 2 h, the reaction was concentrated in vacuo to give the TFA salt of L-norleucine-N-methoxy-N-methylamide as a viscous colorless oil: NMR (CDCl3) δ 0.88 (t, J=7 Hz, 3H), 1.30-1.40 (m, 4H), 1.88 (t, J=7 Hz, 2H), 3.25 (s, 3H), 3.75 (s, 3H), 4.35-4.46 (m, 1H), 7.55-7.76 (br s, 3H). Under nitrogen, the TFA salt was dissolved in 150 mL of chloroform at 0° C. and sequentially treated with 7.37 g (73 mmol) of triethylamine and 5.42 g (55 mmol) of butyl isocyanate. The reaction was allowed to warm to ambient temperature and stir overnight; concentration in vacuo provided the crude product. Purification by silica gel chromatography (Waters Prep-500A) using ethyl acetate gave 9.0 g (90% from N--t--Boc--L--norleucine-N-methoxy-N-methylamide) of the N-butylurea of L-norleucine-N-methoxy-N-methylamide as a colorless oil: NMR (CDCl3) δ 0.83-0.95 (m, 6H), 1.25-1.47 (m, 8H), 1.48-1.60 (m, 1H), 1.63-1.75 (m, 1H), 3.02-3.26 (m, 2H), 3.21 (s, 3H), 3.84 (s, 3H), 4.82-4.93 (m, 1H). Under nitrogen, a 9.0 g (32.5 mmol) sample of the urea was dissolved in 150 mL of anhydrous diethyl ether; the solution was cooled to 0° C. and slowly treated with 41 mL (41 mmol, 1.25 equiv) of a 1.0M solution of lithium aluminum hydride (LAH) in ether. The reaction was allowed to warm to ambient temperature and stir overnight. A solution of 7.87 g (58 mmol) of potassium bisulfate in 165 mL of water was added cautiously and the reaction stirred for 4 h. The reaction mixture was transferred to a separatory funnel and the phases separated. The aqueous phase was extracted 3 times with additional ether. The combined ether extracts were washed 3 times each with 3N hydrochloric acid, saturated sodium bicarbonate, and brine. The ether extracts were then dried (MgSO4) and concentrated in vacuo to give 5.40 (85%) of 3,5-dibutylimidazol-2-one as a viscous colorless oil which solidified on storage in the refrigerator: NMR (CDCl3) δ 0.91 (t, H=7 Hz, 3H), 0.93 (t, J=7 Hz, 3H), 1.28-1.41 (m, 4H), 1.47-1.65 (m, 4H), 2.36 (td, J=7 and 1 Hz, 2H), 3.55 (t, J=7 Hz, 2H), 5.84 (t, J=1 Hz, 1H), 9.78 (br s, 1H).

1. temperatureto warm to ambient temperature
2. stirringthe reaction stirred for 4 h
3. customThe reaction mixture was transferred to a separatory funnel
4. customthe phases separated
5. extractionThe aqueous phase was extracted 3 times with additional ether
6. washThe combined ether extracts were washed 3 times each with 3N hydrochloric acid, saturated sodium bicarbonate, and brine
7. dry with materialThe ether extracts were then dried (MgSO4)
8. concentrationconcentrated in vacuo