反应详情

To a solution of (S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]cyclohexanepropanoic acid (93 g., 343 mmole) in dry tetrahydrofuran (1 l.) was added a 20% molar excess of 1,1'-carbonyldiimidazole over a period of less than 10 minutes with very efficient stirring to keep the internal temperature below 30°. After stirring for 30 minutes, N,O-dimethylhydroxylamine hydrochloride (36.8 g., 377 mmole) was added, followed by triethylamine (38.2 g., 377 mmole). After stirring at room temperature for 4 hours, the reaction mixture was filtered and the resulting filtrate was concentrated in vacuo. The amber colored residue (100 g.) was dissolved in ether (900 ml.) and poured into 1N HCl (1 l.). The acidic aqueous phase was separated, further extracted with ether and the combined ethereal solutions were washed with water, saturated sodium bicarbonate, water, and brine, then dried (MgSO4) to give (S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-N-methoxy-N-methylcyclohexanepropanamide as a colorless oil. [α]D =-12.9° (c=1, methanol). TLC (silica gel; 1:1, ethyl acetate:hexanes) Rf =0.58.

1. customthe internal temperature below 30°
2. stirringAfter stirring for 30 minutes
3. stirringAfter stirring at room temperature for 4 hours
4. filtrationthe reaction mixture was filtered
5. concentrationthe resulting filtrate was concentrated in vacuo
6. dissolutionThe amber colored residue (100 g.) was dissolved in ether (900 ml.)
7. additionpoured into 1N HCl (1 l.)
8. customThe acidic aqueous phase was separated
9. extractionfurther extracted with ether
10. washthe combined ethereal solutions were washed with water, saturated sodium bicarbonate, water, and brine
11. dry with materialdried (MgSO4)