Diethyl (ethoxymethylene)malonate → Diethyl 2-(6-trifluoromethyl-2-pyridylaminomethylene)malonate

HRID 1061739Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=1.C(O[CH:15]=[C:16]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:17]([O:19][CH2:20][CH3:21])=[O:18])C>O1CCOCC1>[CH2:20]([O:19][C:17](=[O:18])[C:16](=[CH:15][NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:9])([F:11])[F:10])[N:3]=1)[C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH3:21]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-amino-6-trifluoromethylpyridine (15.0 g, 92.5 mmol) and diethyl ethoxymethylenemalonate (18.5 mL, 20.0 g, 92.5 mmol) in 1,4-dioxane (30 mL) was stirred at 100° C. for 48 h. Upon cooling to room temperature, 2-[(6-trifluoromethylpyridin-2-ylamino)methylene]malonic acid diethyl ester precipitated from solution, which was separated by filtration, washed with diethyl ether and air-dried (27.2 g, 89%): δH (400 MHz, CDCl3) 1.35 (3H, t, J 7.2), 1.39 (3H, t, J 7.0), 4.28 (2H, q, J 7.2), 4.33 (2H, q, J 7.2), 7.03 (1H, d, J 8.2), 7.38 (1H, d, J 7.4), 7.82 (1H, t, J 8.1), 9.12 (1H, d, J 12.9), 11.20 (1H, d, J 12.5). m/z (ES+) 333 [MH]+, 287 [M-EtO]+

Workup

temperatureUpon cooling to room temperature
custom2-[(6-trifluoromethylpyridin-2-ylamino)methylene]malonic acid diethyl ester precipitated from solution, which
customwas separated by filtration
washwashed with diethyl ether
customair-dried (27.2 g, 89%)

Sources & evidence

ORD record: ord-37d77ca1ea084f8d97e0c14585f610f1
Source dataset: uspto-grants-2005_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06960598B2

Reaction notes

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