4-Methylmorpholine → 4(S)-t-Butoxycarbonylamino-N-ethyl-3(S)-hydroxy-6-methylheptanamide

275 mg (1 mmole) of 4(S)-t-butoxycarbonylamino-3(S)-hydroxy-6-methylheptanoic acid and 197 mg (1.1 mmole) of N-hydroxy-5-norbornene-2,3-dicarboximide were dissolved in 10 ml of methylene chloride and ice-cooled. To this solution were added 227 mg (1.1 mmole) of dicyclohexylcarbodiimide, and the mixture was stirred for 1 hour whilst ice-cooling and for a further 2 hours at room temperature. 90 mg (1.1 mmole) of ethylamine hydrochloride and 111 mg (1.1 mmole) of N-methylmorpholine were then added and the reaction mixture was stirred overnight at room temperature. The precipitated dicyclohexylurea was removed by filtration, and the filtrate was concentrated by evaporation under reduced pressure. A 10% w/v aqueous solution of citric acid was added to the resulting residue, and the precipitated oily substance was extracted with ethyl acetate. The organic extract was washed with, in turn, a 10% w/v aqueous solution of citric acid, water, a 5% w/v aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. Diethyl ether was added to the oily residue to remove insoluble matter, and the filtrate was concentrated by evaporation under reduced pressure. Hexane was added to the resulting oily residue, to solidify it, and the solid was reprecipitated from a 2:1 by volume mixture of hexane and diethyl ether and filtered to give the title compound as a white powdery solid melting at 103°-107° C., [α]23 -43.6° (C=0.5, methanol).

1. temperatureice-cooled
2. stirringthe reaction mixture was stirred overnight at room temperature
3. customThe precipitated dicyclohexylurea was removed by filtration
4. concentrationthe filtrate was concentrated by evaporation under reduced pressure
5. additionwas added to the resulting residue
6. extractionthe precipitated oily substance was extracted with ethyl acetate
7. extractionThe organic extract
8. washwas washed with, in turn
9. dry with materiala 10% w/v aqueous solution of citric acid, water, a 5% w/v aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate
10. concentrationconcentrated by evaporation under reduced pressure
11. additionDiethyl ether was added to the oily residue
12. customto remove insoluble matter
13. concentrationthe filtrate was concentrated by evaporation under reduced pressure
14. additionHexane was added to the resulting oily residue
15. customthe solid was reprecipitated from a 2:1 by volume mixture of hexane and diethyl ether
16. filtrationfiltered

ORD record

ord-b4fc41e4f83f42bfbe9f8f8b78d15dd7

Source dataset

uspto-grants-1987_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04698329