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

Temperature

-30 °C

Tetrahydrofuran was charged to lithium granules (7.6 g) under an argon atmosphere and the mixture cooled to −30° C. 2-Chlorotoluene (69.4 g) was slowly added at −30° C. The reaction was held at −30° C. for 6 hours then added to a suspension of 2-(4-bromophenyl)-1,3,4-oxadiazole (124.4 g) in tetrahydrofuran (800 g) at −65° C. The reaction was held at −65° C. for 30 minutes then a solution of n-hexyllithium (33% w/w in hexanes, 245 ml) was added at −65° C. The reaction was held at −65° C. for 30 minutes and then trimethylborate (230.8 g) was added at −65° C. The reaction was held at −65° C. for 30 minutes then methanol (175 ml) was added followed by 4-methyl-2-pentanone (600 g). The reaction mixture was warmed and the low boiling solvents distilled off under vacuum to a maximum temperature of 50° C. The reaction mixture was cooled to 5-10° C. and the pH adjusted to 6.5 by the addition of 5% w/w sulphuric acid (990.5 g). Product precipitated. The mixture was heated to 40° C. then cooled back to 10° C. Product was isolated, washed with THF and water, and dried yielding the title compound (79.3 g, 75.5%).

1. waitThe reaction was held at −65° C. for 30 minutes
2. waitThe reaction was held at −65° C. for 30 minutes
3. waitThe reaction was held at −65° C. for 30 minutes
4. temperatureThe reaction mixture was warmed
5. distillationthe low boiling solvents distilled off under vacuum to a maximum temperature of 50° C
6. temperatureThe reaction mixture was cooled to 5-10° C.
7. additionthe pH adjusted to 6.5 by the addition of 5% w/w sulphuric acid (990.5 g)
8. customProduct precipitated
9. temperatureThe mixture was heated to 40° C.
10. temperaturethen cooled back to 10° C
11. customProduct was isolated
12. washwashed with THF and water
13. customdried

ORD record

ord-5d4d3091c01c4d92a9eb2a9731de42eb

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07626020B2