Methanol → 2-(3-chlorophenyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one

HRID 1508907Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](=[NH:7])[NH2:6].[F:11][C:12]([F:22])([F:21])[C:13](=O)[CH2:14][C:15](OCC)=[O:16].C[O-].[Na+].CO>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[NH:6][C:15](=[O:16])[CH:14]=[C:13]([C:12]([F:22])([F:21])[F:11])[N:7]=2)[CH:8]=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A 500-mL round bottomed flask was charged with 3-chlorobenzimidamide (4.81 g, 25.3 mmol), ethyl 4,4,4-trifluoro-3-oxobutanoate (5.00 g, 27.1 mmol), and ethanol (90 mL) and cooled to 0° C. A 25% sodium methoxide solution in methanol (13.0 mL, 55.3 mmol) was added to the mixture. The resulting mixture was stirred at reflux for 20 h. After this time, the mixture was cooled to room temperature and concentrated under reduced pressure to 25 mL. The residual slurry was cautiously treated with 2N HCl (50 mL) forming a solid. The solid was collected by filtration and washed with water followed by ether to afford the title compound (3.60 g, 48%) as a white solid, which was carried forward into the next step without further purification. MW=274.63. 1H NMR (DMSO-d6, 500 MHz) δ 13.39 (s, 1H), 8.18 (s, 1H), 8.10 (d, J=7.5 Hz, 1H), 7.73-7.69 (m, 1H), 7.60 (t, J=8.0 Hz, 1H), 6.94 (s, 1H).

Workup

temperatureat reflux for 20 h
temperatureAfter this time, the mixture was cooled to room temperature
concentrationconcentrated under reduced pressure to 25 mL
additionThe residual slurry was cautiously treated with 2N HCl (50 mL)
customforming a solid
filtrationThe solid was collected by filtration
washwashed with water

Sources & evidence

ORD record: ord-8d6573d9cedf45149ba4e3cd1e79c8a7
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

Loading…