p-Toluenesulfonic acid monohydrate → HCID 58000072, compound

HRID 2364125Notes

Reaction equation

[NH2:1]/[C:2](=[CH:8]\[C:9]([O:11][CH2:12][CH3:13])=[O:10])/[C:3]([O:5][CH2:6][CH3:7])=[O:4].CC1C=CC(S(O)(=O)=O)=CC=1.O.[F:26][C:27]1[CH:37]=[CH:36][C:30]([CH2:31][C:32](=[CH2:35])[CH:33]=O)=[CH:29][CH:28]=1>CCCCO>[F:26][C:27]1[CH:37]=[CH:36][C:30]([CH2:31][C:32]2[CH:35]=[C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[N:1][CH:33]=2)=[CH:29][CH:28]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of diethyl 2-aminofumarate (153 g, 0.81 mol) and p-TsOH.H2O (1.5 g, 8.1 mmol) in n-BuOH (325 mL) was added 2-(4-fluorobenzyl)propenal (162 g, 0.98 mol) dropwise at 120° C. The mixture was stirred for 17 h at 120° C. and at rt for ca. 24 h. The mixture was filtered and concentrated under vacuum to yield the crude diethyl 5-(4-fluorobenzyl)-2,3-pyridinedicarboxylate. This material was dissolved in EtOH (400 mL) and an ice-cold solution of NaOH (88 g, 2.2 mol) in water (300 mL) was added. The mixture was stirred for 2 h at rt. After removal of EtOH in vacuo, water (400 mL) and 6N HCl (200 mL) were added and the mixture was extracted with EtOAc. The EtOAc layer was washed with water and the combined aqueous layers adjusted to pH 2 with 6N HCl (175 mL). The mixture was stirred for 1 h at ice-bath temperature and the product was collected by filtration: 1H NMR (d6-DMSO) δ 8.64 (1H, d, J=2 Hz), 8.01 (1H, d, J=2 Hz), 7.32 (2H, dd, J˜9, 6 Hz), 7.12 (2H, t, J˜9 Hz), 4.05 (2H, s); ES+ MS: 276 (M+H+, 100).

Workup

filtrationThe mixture was filtered
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-3325d47d97fd45e19ef33876c8f8e233
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691991B2

Reaction notes

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