Diethyl squarate → 3-ethoxy-4-[2-hydroxy-3-((R)-3-hydroxypyrrolidine-1-carbonyl)phenylamino]cyclobut-3-ene-1,2-dione

HRID 1528158Notes

Reaction equation

[NH2:1][C:2]1[C:3]([OH:16])=[C:4]([C:8]([N:10]2[CH2:14][CH2:13][C@@H:12]([OH:15])[CH2:11]2)=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH2:17]([O:19][C:20]1[C:21](=O)[C:22](=[O:27])[C:23]=1[O:24]CC)[CH3:18]>C(O)C>[CH2:17]([O:19][C:20]1[C:23](=[O:24])[C:22](=[O:27])[C:21]=1[NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([N:10]2[CH2:14][CH2:13][C@@H:12]([OH:15])[CH2:11]2)=[O:9])[C:3]=1[OH:16])[CH3:18]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 3.63 g (16 mmol, 1 eq) of (3-amino-2-hydroxyphenyl)-((R)-3-hydroxypyrrolidin-1-yl)methanone and 3.40 g (20 mmol, 1.2 eq) of 3,4-diethoxy-3-cyclobutene-1,2-dione in 70 ml of ethanol was heated at 60° C. for 16 hours. The reaction medium was filtered and the filtrate was chromatographed on silica gel (column puriFlash IR-50SI-300G, Spot II with solid deposition) eluted with dichloromethane/methanol (gradient). 3.67 g of 3-ethoxy-4-[2-hydroxy-3-((R)-3-hydroxypyrrolidine-1-carbonyl)phenylamino]cyclobut-3-ene-1,2-dione were obtained in the form of a beige solid. Yield=66%.

Workup

filtrationThe reaction medium was filtered
customthe filtrate was chromatographed on silica gel (column puriFlash IR-50SI-300G, Spot II with solid deposition)
washeluted with dichloromethane/methanol (gradient)

Sources & evidence

ORD record: ord-93da9ace2d244d92bce40acd58d9f0b9
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090596B2

Reaction notes

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