2-Chlorotoluene → [4-(1,3,4-oxadiazol-2-yl)phenyl]boronic Acid

Participants

Reaction Conditions

Reaction Steps

Tetrahydrofuran (250 g) was charged to a mixture of lithium granules (3.02 g) and biphenyl (0.01 g) under an argon atmosphere and the mixture cooled to −30° C. 2-Chlorotoluene (27.55 g) was slowly added at −30° C. The reaction was held at −30° C. for 6 hours and then cooled to −65° C. A mixture of 2-(4-bromophenyl)-1,3,4-oxadiazole (50.0 g) in THF (300 g) was slowly added at −65° C. The reaction was held at −65° C. for 30 minutes then a solution of n-hexyllithium (33% w/w in hexanes, 86 ml) was added at −65° C. The reaction was held at −65° C. for 30 minutes and then trimethylborate (48.7 g) was added at −65° C. The reaction was held at −65° C. for 10 minutes then methanol (55.3 g) was added followed by 4-methyl-2-pentanone (240 g). The reaction mixture was warmed and the low boiling solvents distilled off under vacuum to a maximum temperature of 55° C. The residual mixture was cooled to 0° C. and 10% w/w sulphuric acid (92 g) was added followed by water (92 g) whilst maintaining the temperature below 7° C. Product precipitated. The pH was adjusted to 6.5 by the addition of more 10% w/w sulphuric acid (85.3 g). The mixture was heated to 40° C. then cooled back to 5-10° C. Product was isolated and washed with THF (56 g) and water (60 g), yielding wet title compound (25.2 g, 60%).

Provenance & Evidence