反应详情

A mixture of 343 mg (1.51 mmol) of (1S,2R,3S)-3-amino-4-cyclohexyl-1-cyclopropyl-l,2-butanediol, 995mg (1.66mmol) of Fmoc-His(Fmoc)-OH, 0.21 ml (1.61 mmol) of 4-ethylmorpholine, 449 mg (3.22 mmol) of HOBT and 347 mg (1.81 mmol) of EDC in 20 ml of dimethylformamide was left to stand at room temperature overnight. Thereafter, the reaction mixture was evaporated in a high vacuum, the residue was poured into a mixture of ice and 90 ml of sodium bicarbonate solution and extracted three times with 150 ml of ethyl acetate each time. The three ethyl acetate extracts were washed in succession with 70 ml of saturated ammonium chloride solution, 70 ml of 2N sodium bicarbonate solution and 70 ml of saturated sodium chloride solution, combined, dried over magnesium sulphate, filtered and evaporated. The crude product obtained was stirred at room temperature for 3 hours in 60 ml of methylene chloride and 2 ml of piperidine. Then, the reaction mixture was evaporated and the residue was triturated with 50 ml of hexane and filtered off. The filtrate was chromatographed on 70 g of silica gel with a 65:10:1 mixture of methylene chloride, methanol and ammonia as the eluent, whereby there were obtained 390 mg of (S)-α-amino-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]imidazole-4-propionamide as a colourless foam; MS: 365 (M+H)+.

1. waitwas left
2. customThereafter, the reaction mixture was evaporated in a high vacuum
3. additionthe residue was poured into a mixture of ice and 90 ml of sodium bicarbonate solution
4. extractionextracted three times with 150 ml of ethyl acetate each time
5. washThe three ethyl acetate extracts were washed in succession with 70 ml of saturated ammonium chloride solution, 70 ml of 2N sodium bicarbonate solution and 70 ml of saturated sodium chloride solution
6. dry with materialdried over magnesium sulphate
7. filtrationfiltered
8. customevaporated
9. customThe crude product obtained
10. customThen, the reaction mixture was evaporated
11. customthe residue was triturated with 50 ml of hexane
12. filtrationfiltered off
13. customThe filtrate was chromatographed on 70 g of silica gel with a 65:10:1 mixture of methylene chloride, methanol and ammonia as the eluent