Water → N-{2-[(2-amino-ethyl)-ethoxycarbonyl-amino]-1-carboxy-ethyl}-phthalamic acid

온도

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

ORD 기록

ord-f069f803dffa4f499e66b9680141ddcd

출처 데이터셋

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08507476B2