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

HRID 350912Notes

Reaction equation

[F:1][C:2]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:3]=1[CH2:4][O:5][C:6]1[N:7]=[CH:8][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:28]N1C(=O)CCC1=O.ClC(Cl)C(O)=O>ClC(Cl)C>[Cl:28][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])[CH:8]=[N:7][C:6]=1[O:5][CH2:4][C:3]1[CH:23]=[CH:24][C:25]([F:27])=[CH:26][C:2]=1[F:1]

Participants

Conditions

Temperature: 65 °C

Procedure

3-[4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid (from Step 2) (6.62 g, 17.8 mmol), N-chlorosuccinimide (2.85 g, 21.3 mmol), and dichloroacetic acid (4 mL) are combined in dichloroethane (50 mL) and heated at 65° C. for 65 h. The reaction mixture is cooled to 0° C. and the precipitate is filtered, washed with cold dichloroethane, and dried in vacuo. Product obtained as a white solid (3.47 g, 48%). Used without further purification. 1H NMR (CD3OD/300 MHz) δ8.32 (s, 1H), 8.09 (m, 1H), 7.94 (s, 1H), 7.62 (q, 1H, J=8.4 Hz), 7.54 (d, 1H, J=7.8 Hz), 7.03 (m, 2H), 5.61 (s, 2H), 2.21 (s, 3H).

Workup

temperatureThe reaction mixture is cooled to 0° C.
filtrationthe precipitate is filtered
washwashed with cold dichloroethane
customdried in vacuo

Sources & evidence

ORD record: ord-f713496bcb26407b8b8a6c757e7fad3c
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07183287B2

Reaction notes

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