反应详情

温度

65 °C

To a solution of 218.80 g (470.35 mmol) of 3-[(2-tert-butoxycarbonylamino-ethyl)-ethoxycarbonyl-amino]-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester dissolved in 600 mL of tetrahydrofuran was added 100 mL of water and 39.47 g (940.70 mmol) of lithium hydroxide monohydrate. The resulting mixture was heated at 65° C. for 2 h. 19.73 g (470.35 mmol) of lithium hydroxide monohydrate was added. The resulting mixture was stirred at 65° C. for 1 h. The mixture was evaporated to dryness. Toluene was added to the residue and evaporated to dryness to give 225.00 g of the desired compound as a lithium salt. To the resulting lithium salt (225.00 g) suspension in 1 L of dichloromethane was added slowly 500 mL of trifluoroacetic acid. The resulting mixture was stirred at room temperature for 2 h30 and evaporated to dryness. The residue was triturated with a mixture of diethyl ether/dichloromethane and filtered to afford 300.00 g (89%) of a powder. The compound was used as such in the next step.

1. customThe mixture was evaporated to dryness
2. additionToluene was added to the residue
3. customevaporated to dryness