反应详情

(S)-2-(1-(tert-butoxycarbonyl)-4-(8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)piperazin-2-yl)acetic acid (288 mg, 0.61 mmol) can be dissolved in DMF (5 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (222 mg, 1.16 mmol), and 4-Dimethylaminopyridine (48 mg, 0.39 mmol) can be added respectively at room temperature under nitrogen. After about fifteen minutes R-(−)-2-Methyl-2,4-pentanediol (92 mg, 0.78 mmol) can be added and the mixture should be heated to about 50 C under nitrogen. The product can be purified by flash chromatography using 10% Acetone/Dichloromethane as the eluent to give (S)-tert-butyl 4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-2-(2-((R)-4-hydroxy-4-methylpentan-2-yloxy)-2-oxoethyl)piperazine-1-carboxylate. (S)-tert-butyl 4-((E)-8-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-2-(2-((R)-4-hydroxy-4-methylpentan-2-yloxy)-2-oxoethyl)piperazine-1-carboxylate can be dissolved in dichloromethane (1.1 ml) and cooled in an ice bath. Trifluoroacetic acid (0.5 ml) should be added drop wise under nitrogen and slowly allowed to reach room temperature while running overnight. The mixture should be concentrated under vacuum and purified by flash chromatography using 10% Acetone/Dichloromethane as the eluent to give Compound ED.

1. temperaturethe mixture should be heated to about 50 C under nitrogen
2. customThe product can be purified by flash chromatography