Compound 2j

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Synthesis of j-Br: in a round bottom flask, mPEG₇₅₀ (7.50 g, 10.00 mmol) and CBr₄ (3.98 g, 12.00 mmol) were dissolved in 40 mL of acetonitrile. To the stirring solution, PPh₃ (3.15 g, 6.00 mmol) was added in small portions over 30 minutes. The mixture was then left stirring at room temperature for 4 hours. After 4 hours, the solvent was then removed in vacuo and the resulting yellow-orange oil was dissolved in 20 mL of H₂O and left at 4 °C overnight, producing a white precipitate. The mixture was filtered through Celite* on a glass frit and the filtrate was washed twice with 5 mL of toluene. The aqueous layer was dried in vacuo to yield the desired product as an orange oil (7.08 g, 87%). ¹H NMR (400 MHz, CDCl₃): δ 3.55 – 3.51 (m, 62H, CH₂O(CH₂CH₂O)₁₅), 3.43 (m, 2H, BrCH₂), 3.26 (s, 3H, (CH₂CH₂O)₁₅CH₃). Celite was pretreated on the frit by washing with 30 mL of H₂O before the mixture was filtered.

Synthesis of j-Sac: to a solution of j-Br (1.07 g, 1.32 mmol) in 35 mL of ethanol, potassium thioacetate (0.20 g, 1.75 mmol) was added in one portion. The mixture was refluxed at 120 °C for 5 hours. The resulting suspension was filtered through Celite and the filtrate was dried under vacuum, affording a brown oil. The oil was dissolved in 40 mL of chloroform and the organic phase was washed twice with H₂O. The organic layer was dried over Na₂SO₄ and filtered through Celite. The solvent was removed in vacuo, providing j-SAc (0.64 g, 74%). ¹H NMR (400 MHz, CDCl₃): δ 3.64 – 3.61 (m, 62H, CH₂O(CH₂CH₂O)₁₅), 3.36 (s, 3H, (CH₂CH₂O)₁₅CH₃), 3.07 (t, 2H, SCH₂), 2.32 (s, 3H, SCOCH₃).

Synthesis of j: j-SAc (405 mg, 0.5 mmol) was charged with 5 mL of 1M HCl and was refluxed at 110 °C for 2 hours under a blanket of Ar. The solvent was removed in vacuo. The residue was dissolved in 10 mL of DCM and the organic phase was washed twice with water. The organic layer was separated and dried over Na₂SO₄ and filtered through Celite. The solution was dried under vacuum to yield the desired product as a brown oil (319 mg, 83%). Product was stored under inert atmosphere. ¹H NMR (400 MHz, CD₂Cl₂): δ 3.58 – 3.59 (m, 62H, CH₂O(CH₂CH₂O)₁₅), 3.32 (s, 3H, (CH₂CH₂O)₁₅CH₃), 2.67 (dt, 2H, SHCH₂), 1.61 (t, 1H, SHCH₂).

Synthesis of 2j: 2 (5.0 mg, 0.0020 mmol) and K₃PO₄ (19.2 mg, 0.090 mmol) were added along with a flea micro stir bar to a 4-mL glass vial, which was then sealed with a PTFE/silicone cap under ambient conditions. The vial was then purged and backfilled with N₂ three times before being transferred into the glovebox. In the glovebox, the vial was opened and 150 µL anhydrous DMF was added, followed by mPEGthiol₇₆₆ (48.1 µL, 0.069 mmol). The vial was sealed again and set to stir at 400 rpm for 24 hours. The vial was transferred out of the glovebox, and its contents were transferred into an NMR tube for in situ ¹⁹F NMR spectroscopy to ensure nearly quantitative conversion and in situ ¹¹B NMR spectroscopy to ensure structural integrity of the cluster. The crude mixture was then transferred into a 20-mL glass vial and lyophilized for solvent removal. A 1.25 cm x 35 cm glass column was packed with Sephadex G50 medium in water (23 cm packed height), and the crude product mixture containing 2j was loaded onto the column with water. 15 1-2 mL fractions were collected, dried via lyophilization, and subjected to characterization via ¹H, ¹¹B, and ¹⁹F NMR spectroscopy. The pure product fractions as indicated by NMR spectroscopy were combined and dried via lyophilization to obtain an isolated yield of 4.4 mg (19 %). ¹H NMR (400 MHz, CD₃OD): δ 5.50 (br s, 24H, OCH₂), 3.63 – 3.53 (m, 744H, SCH₂CH₂O(CH₂CH₂O)₁₅), 3.35 (m, 36H, (CH₂CH₂O)₁₅CH₃), 3.08 (t, 24H, SCH₂). ¹¹B NMR (128 MHz, CD₃OD): δ -16.0. ¹⁹F NMR (376 MHz, CD₃OD): δ -137.2 (m, 24F, -meta), -144.8 (m, 24F, -ortho).