Morpholine → HCID 68785689, compound

HRID 2265978Notes

Reaction equation

[C:1]([C:5]1[N:10]=[C:9](Cl)[C:8]([CH:12]=[CH:13][C:14]([O:16][CH3:17])=[O:15])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.CCN(CC)CC>CN(C=O)C.[Pd]>[CH3:17][O:16][C:14](=[O:15])[CH:13]=[CH:12][C:8]1[C:9]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

3-(6-tert-Butyl-2-chloro-pyridin-3-yl)-acrylic acid, methyl ester (0.28 μg, 1.11 mmol) was dissolved in DMF, and morpholine (0.15 ml), NEt3 (0.31 ml) and palladium reagent (48 mg) were added stepwise and then the reaction mixture was stirred at 80° C. for 18 hours. The resulting mixture was extracted with EtOAc, and the organic phase was dried over anhydrous MgSO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (Hex/EtOAc=8/1) to give 3-(6-tert-butyl-2-morpholin-4-yl-pyridin-3-yl)-acrylic acid methyl ester (76 mg, 0.25 mmol, 22.5%). The methyl ester was dissolved in 1,4-dioxane, treated with water and KOH, stirred and heated at reflux for 18 hrs. The reaction mixture was cooled to room temperature, diluted with water, and then washed with ether. The aqueous phase was acidified with 1N HCl, and then extracted with EtOAc, and the combined organic phase was washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure to give 3-(6-tert-butyl-2-morpholin-4-yl-pyridin-3-yl)-acrylic acid (67 mg, 92%).

Workup

extractionThe resulting mixture was extracted with EtOAc
dry with materialthe organic phase was dried over anhydrous MgSO4
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by column chromatography (Hex/EtOAc=8/1)

Sources & evidence

ORD record: ord-70b6ff466b3641dfa9a6cca8ff4e9a3d
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858621B2

Reaction notes

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