Diethyl (ethoxymethylene)malonate → HCID 89582867, compound

HRID 2272726Notes

Reaction equation

[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[CH2:9]([N:11]=[C:12]=[O:13])[CH3:10].C(O[CH:17]=[C:18]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:19]([O:21]CC)=O)C.CC[O-].[Na+]>C1COCC1.C(O)C>[CH2:27]([O:26][C:24]([C:18]1[C:19](=[O:21])[N:11]([CH2:9][CH3:10])[C:12](=[O:13])[N:6]([C:5]2[CH:7]=[CH:8][C:2]([F:1])=[CH:3][CH:4]=2)[CH:17]=1)=[O:25])[CH3:28]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-fluoroaniline (1.0 g, 9.01 mmol) in THF (20 mL) at 0° C., was slowly added ethyl isocyanate (0.70 g, 10.0 mmol). After stirring 30 min. at 0° C., the solution was warmed to rt and the solvent was removed under vacuum. To the residue was added ethanol (30 mL), diethyl ethoxymethylenemalonate (1.95 g, 9.01 mmol) and 21% NaOEt in ethanol (2.92 mL, 9.01 mmol)) and the reaction stirred 48 h at rt. The solvent was removed under vacuum and cold conc. HCl was added to pH 6. The aqueous layer was removed under vacuum and the solids were crystallized from ethyl acetate and hexanes. 3-Ethyl-1-(4-fluorophenyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester isomer was isolated in 25% yield. 1H NMR (CDCl3) δ: 8.32 (s, 1H), 7.20-7.14 (m, 4H), 4.35 (q, 2H, J=7.1 Hz), 3.95 (q, 2H, J=7.2 Hz), 1.42 (t, 3H, J=7.2 Hz), 1.36 (t, 3H, J=7.2 Hz).

Workup

customat 0° C.
temperaturethe solution was warmed to rt
customthe solvent was removed under vacuum
stirringstirred 48 h at rt
customThe solvent was removed under vacuum and cold conc. HCl
additionwas added to pH 6
customThe aqueous layer was removed under vacuum
customthe solids were crystallized from ethyl acetate and hexanes

Sources & evidence

ORD record: ord-1750abc0c74d42de89733e4a0bd36826
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09120778B2

Reaction notes

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