Dichloroacetic Acid → 3-(5-chloro-4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid

HRID 1713253Notes

Reaction equation

[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][O:5][C:6]1[N:7]=[C:8]([CH3:23])[N:9]([C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:16]([OH:18])=[O:17])[C:10](=[O:12])[CH:11]=1.[Cl:29]N1C(=O)CCC1=O.ClC(Cl)C(O)=O>C(#N)C>[Cl:29][C:11]1[C:10](=[O:12])[N:9]([C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=2[CH3:22])[C:16]([OH:18])=[O:17])[C:8]([CH3:23])=[N:7][C:6]=1[O:5][CH2:4][C:3]1[CH:24]=[CH:25][C:26]([F:28])=[CH:27][C:2]=1[F:1]

Participants

Conditions

Temperature: 70 °C

Procedure

To a suspension of 3-[4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid (1.0 g, 2.6 mmol) in anhydrous acetonitrile (15 mL) was added N-chlorosuccinimide (0.38 g, 2.9 mmol) and dichloroacetic acid (0.2 mL, 2.6 mmol). The reaction was heated in oil bath (70° C.) overnight under nitrogen. The reaction mixture was concentrated under reduced pressure to remove acetonitrile. The resulting residue was washed with water for 30 min, filtered, and rinsed with water. The white solid (830 mg, 82%) was dried in vacuo. 1H-NMR (CD3OD, 400 MHz) δ 8.09 (dd, 1H, J=1.6 Hz), 7.88 (d, 1H, J=2 Hz), 7.56 (m, 2H), 7.01 (m, 2H), 5.57 (s, 2H), 2.16 (s, 3H), 2.13 (s, 3H); ES-HRMS m/z 421.0753 (M+H C20H16ClF2N2O4 requires 421.0761).

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
customto remove acetonitrile
washThe resulting residue was washed with water for 30 min
filtrationfiltered
washrinsed with water
dry with materialThe white solid (830 mg, 82%) was dried in vacuo

Sources & evidence

ORD record: ord-5006e0172e104a95b4fd2ab8cdf2bbf0
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795271B2

Reaction notes

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