Toluene → 2,3-Dihydro-1-methyl-3-(phenylmethyl)-2-thioxo-6-(trifluoromethyl)-4(1H)-pynmidinone

HRID 584557Notes

Reaction equation

[F:1][C:2]([F:13])([F:12])[C:3]([NH:10][CH3:11])=[CH:4][C:5]([O:7]CC)=O.[H-].[Na+].[N-:16]=[C:17]=[S:18].[C:19]1([CH3:25])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[CH3:11][N:10]1[C:3]([C:2]([F:1])([F:13])[F:12])=[CH:4][C:5](=[O:7])[N:16]([CH2:25][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:17]1=[S:18]

Participants

Conditions

Temperature: -50 °C

Procedure

4,4,4-Trifluoro-3-(methylamino)-2-butenoic acid, ethyl ester, (2Z)-(1.43 g) in toluene (25 ml) was slowly added to a stirred suspension of sodium hydride (60%, 0.28 g) in anhydrous N,N-dimethylformamide (25 ml) at −10° C. The solution was stirred for 0.5 hr at this temperature and cooled to −50° C. The above isothiocyanate dissolved in toluene (25 ml) was added drop wise with stirring to the solution, while maintaining the temperature at −50° C. The solution was then allowed to warm to −20° C. and stirred for 2 hr. After neutralization with dilute hydrochloric acid, the solution was partitioned between water and ethyl acetate and the organic layer was evaporated to furnish a crude product. Column chromatography over silica gel (eluent, hexane:ethyl acetate, 90:10) afforded the title compound (2.6 g). 1H NMR, CDCl3, 3.86 (3H, m), 5.74 (2H, s), 6.51 (1H, s), 7.27-7.30 (3H, m), 7.42-7.46 (2H, m).

Workup

additionwas added drop wise
stirringwith stirring to the solution
temperaturewhile maintaining the temperature at −50° C
temperatureto warm to −20° C.
stirringstirred for 2 hr
customAfter neutralization with dilute hydrochloric acid, the solution was partitioned between water and ethyl acetate
customthe organic layer was evaporated
customto furnish a crude product

Sources & evidence

ORD record: ord-6d8734c7a59b43f5a181dea6e9fc2827
Source dataset: uspto-grants-2005_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06927193B2

Reaction notes

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