Phosphorus oxychloride → 1-(2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanone

HRID 1521506Notes

Reaction equation

[C:1](/[C:4](/[C:10](=O)[C:11]([F:14])([F:13])[F:12])=[CH:5]\[NH:6][C:7]([NH2:9])=O)(=[O:3])[CH3:2].O=P(Cl)(Cl)[Cl:18]>O>[Cl:18][C:7]1[N:9]=[C:10]([C:11]([F:14])([F:13])[F:12])[C:4]([C:1](=[O:3])[CH3:2])=[CH:5][N:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of compound (E)-1-(2-acetyl-4,4,4-trifluoro-3-oxobut-1-en-1-yl)urea (55 g, 0.25 mol) and POCl3 (240.7 g, 1.57 mol) was stirred at 100° C. for 3 h. The mixture was added dropwise to water (1.5 L) at rt and extracted with EtOAc (3×500 mL). The combined organic layers were washed with brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography eluting with PE/EtOAc 3/1 to give compound 1-(2-chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanone (23.5 g, 42.7% yield) as a pale-yellow oil. 1H NMR (CDCl3 300 MHz): δ 8.80 (s, 1H), 2.58 (s, 3H). 19F NMR (920-083-1A CDCl3 400 MHz): δ-65.5 ppm. 13C NMR (903-158-1A CDCl3 400 MHz): δ 195.9, 162.3, 160.1, 153.8 (dd, J=50 Hz), 130.9, 119.5 (dd, J=366 Hz), 30.7.

Workup

extractionextracted with EtOAc (3×500 mL)
washThe combined organic layers were washed with brine (500 mL)
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by column chromatography
washeluting with PE/EtOAc 3/1

Sources & evidence

ORD record: ord-8f7aaa915a334637ab5b2e9756b1cf63
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073931B2

Reaction notes

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