Ethanol → Diethyl 2-(((3-(3,5-dimethylisoxazol-4-yl)-4-methoxyphenyl)amino)methylene)malonate

HRID 81974Notes

Reaction equation

[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([NH2:15])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])=[C:5]([CH3:16])[O:4][N:3]=1.C(O[CH:20]=[C:21]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:22]([O:24][CH2:25][CH3:26])=[O:23])C.C(O)C>C(Cl)Cl>[CH2:25]([O:24][C:22](=[O:23])[C:21](=[CH:20][NH:15][C:9]1[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([C:6]2[C:2]([CH3:1])=[N:3][O:4][C:5]=2[CH3:16])[CH:8]=1)[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH3:26]

Participants

Conditions

Temperature: 130 °C

Procedure

[3-(3,5-Dimethyl-4-isoxazolyl)-4-(methyloxy)phenyl]amine (for a preparation see Intermediate 2) (39 g, 179 mmol) was dissolved in diethyl [(ethyloxy)methylidene]propanedioate (38.6 g, 179 mmol) and heated to 130° C., giving a steady effervescence as ethanol boiled off. The solution was heated for 1 h, then cooled to room temperature and evaporated in vacuo to give a brown oil. The product was dissolved in DCM (100 ml) and loaded onto a 750 g silica column, then eluted with 0-100% EtOAc/cyclohexane to give diethyl({[3-(3,5-dimethyl-4-isoxazolyl)-4-(methyloxy)phenyl]amino}methylidene)propanedioate (59.5 g, 153 mmol, 86% yield) as pale yellow crystalline solid. LCMS (formate) Rt 1.15 min, MH+ 389.

Workup

temperatureThe solution was heated for 1 h
temperaturecooled to room temperature
customevaporated in vacuo
customto give a brown oil
washeluted with 0-100% EtOAc/cyclohexane

Sources & evidence

ORD record: ord-4d552f4342a8488da96c533a7bf87f46
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846709B2

Reaction notes

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