Xphos (HPMC encapsulated)

• 4-Bromoanisole [B0547]
• Potassium Phenyltrifluoroborate [P1582]
• Cesium Carbonate [C2160]
• Pd₂(dba)₃ (HPMC encapsulated) [R0305]
• XPhos (HPMC encapsulated) [R0302]
• THF

Pd₂(dba)₃ (HPMC encapsulated) (one capsule) and XPhos (HPMC encapsulated) (one capsule) were added to a solution of 4-bromoanisole (1.21 g, 6.47 mmol), cesium carbonate (6.32 g, 19.4 mmol, 3 eq.) and potassium phenyltrifluoroborate (1.43 g, 7.76 mmol, 1.2 eq.) in THF/water (4:1, 20 mL) at r.t. and the reaction mixture was stirred at 65 °C for 2 hours. The solution was then diluted with ethyl acetate (15 mL) and sat. Na₂SO₄ aq. (15 mL), and filtered through Celite pad. The filtrate was extracted with ethyl acetate (10 mL x 2) and 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 (hexane) to afford 4-methoxybiphenyl (1.09 g, 90% yield) as a white solid.

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 XPhos (ca. 125 μmol) and Pd₂(dba)₃ (ca. 60 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.

4-Methoxybiphenyl

¹H NMR (400 MHz, CDCl₃); δ 7.55-7.50 (m, 4H), 7.42-7.38 (t, J = 7.6 Hz, 2H), 7.31-7.27 (t, J = 7.6 Hz,1H), 6.98-6.95 (d, J = 9.2 Hz, 2H), 3.84 (s, 3H).

• 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.