Trimethyl borate → HCID 57974745, compound

Temperature

0 °C

Dry THF (4 mL) is cooled to at −3° C. under nitrogen. BuMgCl (0.6 mL, 1.2 mmol, 2M in THF) is added. n-BuLi (1.5 mL, 2.4 mmol, 1.6 M in hexanes) is then added dropwise over 20 min at −3° C. to 0° C. After the addition, the solution is stirred at 0° C. for 45 min. The solution is cooled to −45° C. and treated dropwise over 20 min at −45 to −40° C. with a solution of 2-(4-bromophenyl)benzenecarbonitrile (0.5 g, 1.9 mmol) in a total of 4 mL THF. The resulting yellowish-orange solution is allowed to warm to −25° C. over 1 h. After 1 h, the solution is cooled to −73° C. Trimethylborate (0.43 mL, 3.87 mmol) is added dropwise over 15 min at −73° C. The solution is stirred 1 h at −73° C. The reaction is allowed to warm to −63° C. The reaction is quenched with 5 mL of 1N HCl and allowed to warm to 0° C. with stirring. The mixture is extracted with 10 mL ethyl acetate. The organic solution is shaken with brine, dried (Na2SO4).and concentrated to obtain 0.435 g of crude product. This in 5 mL of 1:1 toluene/heptane is heated to 95° C. with stirring for 10 min. Upon cooling to rt and then to 10° C., the solid is collected by filtration and rinsed three times 1:1 toluene/heptane. The solid is vacuum-dried to provide title compound (0.232 g, 95.65% HPLC, Hitachi 7000 series, SB phenyl column, 218 nm, 65% MeCN/35% water with 0.05% TFA, 1 mL/min).

1. additionAfter the addition
2. temperatureThe solution is cooled to −45° C.
3. temperatureto warm to −25° C. over 1 h
4. waitAfter 1 h
5. temperaturethe solution is cooled to −73° C
6. stirringThe solution is stirred 1 h at −73° C
7. temperatureto warm to −63° C
8. customThe reaction is quenched with 5 mL of 1N HCl
9. temperatureto warm to 0° C.
10. stirringwith stirring
11. extractionThe mixture is extracted with 10 mL ethyl acetate
12. stirringThe organic solution is shaken with brine
13. dry with materialdried (Na2SO4)
14. concentration.and concentrated
15. customto obtain 0.435 g of crude product
16. stirringwith stirring for 10 min
17. temperatureUpon cooling to rt
18. filtrationto 10° C., the solid is collected by filtration
19. washrinsed three times 1:1 toluene/heptane
20. customThe solid is vacuum-dried

ORD record

ord-15965d8c728f4adfa8ed0de1b97e977a

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07625932B2