Formic Acid → 4,4'-((Oxybis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-5,2-diyl))bis(2-methylphenol)

Participants

Reaction Conditions

Reaction Steps

An appropriately sized and equipped reaction vessel was charged with 4-iodo-2-methylphenol (75.7 g, 323 mmol) in 380 mL DMF. To that was added Pd(PPh3)4 (3.56 g, 3.08 mmol) at room temperature giving a light yellow solution. Then, 5,5′-(oxybis(ethane-2,1-diyl))bis(bicyclo[2.2.1]hept-2-ene) (39.8 g, 154 mmol), 100 ml dimethylformamide (DMF), and triethylamine (65 mL, 462 mmol) were added and the mixture stirred as formic acid (17.7 g, 14.5 mL 385 mmol) was added drop wise within 5 minutes. The reaction temperature rose from 20° C. to 25° C. after which external heating was applied. At 70° C., an exothermic reaction began and the temperature quickly climbed to 82° C. within 10 minutes accompanied by color changes from light yellow to orange to black. The reaction was monitored by GC and after stirring at 75° C. for 96 h an aliquot GC indicated the reaction was complete. The reaction mixture was allowed to cool to room temperature and was poured into 2000 mL distilled water. The aqueous mixture was extracted with (3×1500 mL) MTBE, the extracts were filtered through a Celite® filtering aid pad to remove palladium particles and then washed with (2×1 L) water, (2×1 L) brine and (2×1 L) 5% aqueous LiCl to remove residual DMF. The resulting MTBE solution was dried over sodium sulfate, filtered, and the solvent rotary evaporated to give 94 g of a brown liquid. The 94 g of crude PP475 was adsorbed onto 120 g silica and chromatographed over an additional 1 kg of silica eluting with heptane-EtOAc mixtures. The concentrated purified fractions yielded 43 g (59% yield) of PP475 as a clear viscous oil with >98.0% purity by NMR. NMR and MS were consistent with the desired structure.

Provenance & Evidence