[1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) Dichloride (HPMC encapsulated)

• 2-Acetamido-5-bromo-4-methylpyridine [A2823]
• Phenylboronic Acid [B0857]
• Cesium Carbonate [C2160]
• Organ's Catalyst (HPMC encapsulated) [R0321]
• THF

Organ's catalyst (HPMC encapsulated) (one capsule) was added to a solution of 2-acetamido-5-bromo-4-methylpyridine (275 mg, 1.20 mmol), cesium carbonate (430 mg, 1.32 mmol, 1.1 eq.) and phenylboronic acid (220 mg, 1.8 mmol, 1.5 eq.) in THF/water (4:1, 5 mL) at room temperature and the reaction mixture was stirred at 100 °C for 2 hours. The solution was then diluted with ethyl acetate (10 mL) and sat. Na₂SO₄ aq. (10 mL), and filtered through Celite pad and the filtrate was extracted with ethyl acetate (10 mL x 2). The organic layer was washed with water (10 mL) and brine (10 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate:hexane = 1:2 - 4:1) and then further purified by reversed-phase silica gel chromatography　(water:acetonitrile = 95:5 - 40:60) to afford 2-acetamido-4-methyl-5-phenylpyridine (227 mg, 84% yield) as a white solid.

The reaction mixture was monitored by GC.
The silica gel column purification failed to separate the debromo compound. Therefore, the purification was also performed on an ODS column.
The material of the capsule is water-soluble HPMC (hydroxypropyl methylcellulose).
The shape of the capsule is like the image below and Organ’s catalyst (ca. 60 μmol) is encapsulated in each capsule.

The capsule disintegrates as shown in the image below when stirred in the solvent for about 15 minutes, releasing its content.

2-Acetamido-4-methyl-5-phenylpyridine

¹H NMR (400 MHz, CDCl₃); δ 9.24-9.06 (brs, 1H), 8.16 (s, 1H), 8.10 (s, 1H), 7.46-7.36 (m, 3H), 7.30-7.29 (m, 2H), 2.32 (s, 3H), 2.21 (s, 3H).

• Reagent and Catalyst Capsules: A Chemical Delivery System for Reaction Screening and Parallel Synthesis
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• HPMC: A Biomass-Based Semisynthetic Sustainable Additive Enabling Clean and Fast Chemistry in Water
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