L-Proline (HPMC encapsulated)

• 2-Bromopyridine [B0650]
• Indole [I0021]
• Cesium Carbonate [C2160]
• Cupper Iodide (HPMC encapsulated) [R0314]
• L-Proline (HPMC encapsulated) [R0313]
• DMSO

Copper(I) iodide (HPMC encapsulated) (one capsule) and L-proline (HPMC encapsulated) (one capsule) were added to a solution of indole (93.7 mg, 800 µmol), 2-bromopyridine (164 mg, 1.04 mmol, 1.3 eq.) and cesium carbonate (521 mg, 1.60 mmol, 2.0 eq.) in DMSO (2.5 mL) at room temperature and the reaction mixture was stirred at 150 °C for 2 hours. After cooling to room temperature, the solution was diluted with ethyl acetate (15 mL) and sat. Na₂SO₄ aq. (15 mL), and filtered through Celite pad and the filtrate was extracted with ethyl acetate (15 mL x 2). The organic layer was washed with 2 mol/L HCl (15 mL) and sat. NaHCO₃ aq. (15 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (ethyl acetate:hexane = 1:10 - 1:5) to afford N-(2-pyridyl)indole (100 mg, 62% yield) as a pale-yellow oil.

The reaction mixture was monitored by UPLC.
The material of the capsule is water-soluble HPMC (hydroxypropyl methylcellulose).
The capsule has the shape shown in Fig. 1 and L-proline (ca. 500 μmol) and copper(I) iodide (ca. 800 μmol) are encapsulated in each capsule, respectively.

Fig. 1. Appearance of capsule

Fig. 2. Capsule disintegrating
(left) Immediately after the addition of the capsule,
(right) 15 minutes after the addition of the capsule.

N-(2-Pyridyl)indole

¹H NMR (400 MHz, CDCl₃); δ 8.21 (d, J = 8.0 Hz, 1H), 7.85-7.81 (m, 1H), 7.37 (d, J = 4.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.30(t, J = 8.0 Hz, 1H), 7.23-7.16 (m, 2H).

• Reagent and Catalyst Capsules: A Chemical Delivery System for Reaction Screening and Parallel Synthesis
  • N. Borlinghaus, J. Kaschel, J. Klee, V. Haller, J. Schetterl, S. Heitz, T. Lindner, J. D. Dietrich, W. M. Braje, A. Jolit, J. Org. Chem. 2021, 86, 1357.

• HPMC: A Biomass-Based Semisynthetic Sustainable Additive Enabling Clean and Fast Chemistry in Water
  • S. Sharma, T. N. Ansari, S. Handa, ACS Sustainable Chem. Eng. 2021, 9, 12719.