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[20240205]

"metallophotoredox C-N cross-coupling reaction of 5-bromopyrimidine and morpholine using the capsule reagent"

Used Chemicals

• 5-Bromopyrimidine  [B2229]
• Morpholine  [M0465]
• Reagents for Metallophotoredox Cross-Coupling Reactions (HPMC encapsulated) (NiBr2(dme), [Ir[dF(CF3)ppy]2(dtbbpy)]PF6, DABCO)  [R0273]
• N,N-Dimethylacetamide (= DMAc)

Procedure

Reagents for metallophotoredox cross-coupling reactions (HPMC encapsulated) (one capsule) was added to a solution of 5-bromopyrimidine (95 mg, 0.60 mmol) and morpholine (78 μL, 0.90 mmol, 1.5 eq.) in DMAc (6 mL) at room temperature. The solution was placed at a distance of 3-5 cm from Blue LED lamp and stirred for 24 hours at 60 °C. The reaction mixture was then filtered through Celite®. The filtrate was diluted with saturated Na2SO4 aq. (15 mL) and extracted with ethyl acetate (15 mL x 5). The organic layer was dried over sodium sulfate, concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (dichloromethane:methanol = 10:1) to afford 4-(pyrimidin-5-yl)morpholine (84 mg, 85% yield) as a pale brown solid.

Experimenter’s Comments

The reaction mixture was monitored by GC.
Irradiation of visible light was performed with Kessil A160WE Tuna Blue 40W x 2.
DMAc was degassed with nitrogen gas for 30 minutes before use.
The shape of the capsule is like below image and each capsule includes NiBr2(dme) (ca. 0.03 mmol), [Ir[dF(CF3)ppy]2(dtbbpy)]PF6 (ca. 0.12 μmol), and DABCO (ca. 1.1 mmol).
The material of the capsule is water-soluble HPMC (hydroxypropyl methylcellulose).

Analytical Data

4-(Pyrimidin-5-yl)morpholine

1H NMR (400 MHz, CDCl3); δ 8.74 (s, 1H), 8.37 (s, 2H), 3.91-3.88 (m, 4H), 3.25-3.22 (m, 4H).

Lead Reference

• Reagent and Catalyst Capsules: A Chemical Delivery System for Reaction Screening and Parallel Synthesis
• • N. Borlinghaus, B. Schönfeld, S, Heitz, J. Klee, S. Vukelić, W. M. Braje, A. Jolit, J. Org. Chem. 2021, 86, 1357.

Other Reference

• 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.