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

HRID 1890409Notes

Reaction equation

CO[C:3](=O)[CH:4]([N:22]1[C:30](=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]1=[O:32])[CH2:5][N:6]([CH2:12][CH2:13][NH:14]C(OC(C)(C)C)=O)[C:7]([O:9][CH2:10][CH3:11])=[O:8].[OH2:34].[OH2:35].[OH-:36].[Li+]>O1CCCC1>[NH2:14][CH2:13][CH2:12][N:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:5][CH:4]([NH:22][C:23](=[O:32])[C:24]1[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:30]([OH:31])=[O:36])[C:3]([OH:35])=[O:34]

Participants

Conditions

Temperature: 65 °C

Procedure

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.

Workup

customThe mixture was evaporated to dryness
additionToluene was added to the residue
customevaporated to dryness

Sources & evidence

ORD record: ord-f069f803dffa4f499e66b9680141ddcd
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507476B2

Reaction notes

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