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]=[CH:8][N:9]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=2[CH3:23])[C:16]([O:18]C)=[O:17])[C:10](=[O:12])[CH:11]=1.[OH-].[Na+]>O1CCOCC1>[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]=[CH:8][N:9]([C:13]2[CH:14]=[C:15]([CH:20]=[CH:21][C:22]=2[CH3:23])[C:16]([OH:18])=[O:17])[C:10](=[O:12])[CH:11]=1Participants
4
Procedure
To a solution of methyl 3-[4-[(2,4-difluorobenzyl)oxy]-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoate (from Step 1) (7.56 g, 19.6 mmol) in dioxane (30 mL) was added 2N NaOH (14.7 mL). Stirred at ambient temperature for 1 h. Concentrated to ˜20 mL under reduced pressure. Cooled to 0° C. and added 5% citric acid to precipitate solid, filtered the precipitate, rinsed with water, and dried in vacuo overnight. Obtained product as an orange solid (6.62 g, 91%). Used without further purification. 1H NMR (CD3OD/400 MHz) δ8.28 (s, 1H), 8.04 (m, 1H), 7.88 (s, 1H), 7.56 (q, 1H, J=8.4 Hz), 7.50 (d, 1H, J=8.0 Hz), 6.99 (m, 2H), 5.87 (s, 1H), 5.39 (s, 2H), 2.19 (s, 3H). ESHRMS m/z 373.1001 (M+H calculated for C19H15F2N2O4 requires 373.0994).
Workup
- concentrationConcentrated to ˜20 mL under reduced pressure
- temperatureCooled to 0° C.
- additionadded 5% citric acid
- customto precipitate solid
- filtrationfiltered the precipitate
- washrinsed with water
- customdried in vacuo overnight
- customUsed without further purification
Sources & evidence
- ORD record
- ord-9092bef6b5ef4b3491396b08565a6873
- Source dataset
- uspto-grants-2007_02
- Patent number
- US07183287B2
Linked notes
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