Citric Acid → 3-[4-[(4-fluoro-2-{[(methoxycarbonyl)amino]methyl}benzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoic Acid

HRID 1867148Notes

Reaction equation

[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][O:7][C:8]2[CH:13]=[C:12]([CH3:14])[N:11]([C:15]3[CH:16]=[C:17]([CH:22]=[CH:23][C:24]=3[CH3:25])[C:18]([O:20]C)=[O:19])[C:10](=[O:26])[CH:9]=2)=[C:4]([CH2:29][NH:30][C:31]([O:33][CH3:34])=[O:32])[CH:3]=1.[OH-].[Na+].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[F:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][O:7][C:8]2[CH:13]=[C:12]([CH3:14])[N:11]([C:15]3[CH:16]=[C:17]([CH:22]=[CH:23][C:24]=3[CH3:25])[C:18]([OH:20])=[O:19])[C:10](=[O:26])[CH:9]=2)=[C:4]([CH2:29][NH:30][C:31]([O:33][CH3:34])=[O:32])[CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To methyl 3-[4-[(4-fluoro-2-{[(methoxycarbonyl)amino]methyl}benzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-4-methylbenzoate (from Step 3) (0.17 g, 0.36 mmol) was added 1.5 N NaOH solution in 1:1 MeOH:water (0.39 mL, 0.59 mmol). The reaction mixture was stirred at 60° C. for 2.5 h. The solution was cooled (0° C.), neutralized by the slow addition of 5% citric acid, and organic products extracted in DCM. A white solid suspended in the organic layer was filtered, washed with DCM and water, dried in vacuo, and found to be the desired product (0.090 g, 55%). 1H NMR (CD3OD/400 MHz) δ8.03 (m, 1H), 7.75 (s, 1H), 7.52 (d, 1H, J=8.0 Hz), 7.47 (m, 1H), 7.12 (m, 1H), 7.03 (m, 1H), 6.21 (s, 1H), 6.08 (s, 1H), 5.18 (s, 2H), 4.38 (s, 2H), 3.65 (s, 3H), 2.12 (s, 3H), 1.90 (s, 3H). ESHRMS m/z 455.1632 (M+H calculated for C24H24FN2O6 requires 455.1613).

Workup

temperatureThe solution was cooled (0° C.)
extractionextracted in DCM
filtrationwas filtered
washwashed with DCM and water
customdried in vacuo

Sources & evidence

ORD record: ord-366b30f5ba3d4be889c10f4c76bfd034
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629363B2

Reaction notes

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