Diisopropylamine → HCID 86727036, compound

Temperature

-78 °C

A solution of diisopropylamine (11.7 mL, 82.0 mmol) in THF (200 mL) was treated with n-butyllithium (33 mL, 82 mmol) at 0° C. The solution was stirred for 30 min before being cooled to −78° C. Next, a solution of 4-bromo-N-tert-butyl-3-fluorobenzamide (9.0 g, 33 mmol) in THF (100 mL) was added. The solution was then warmed to −40° C. and maintained there for 1 h. Next, (R)-(+)-propylene oxide (6.9 mL, 98 mmol) was added and the solution warmed to 0° C. After 1 h, the ice bath was removed and the solution was allowed to warm to rt. LC/MS indicated desired product present. The solution was quenched with MeOH, diluted with brine (200 mL), and extracted with EtOAc (300 mL). The organic layer was removed, dried over MgSO4, filtered and concentrated. The crude material was purified using a 340 g Biotage SNAP (0-60% Hexanes: EtOAc) cartridge to yield the title compound. LC-MS: m/z 332.08 (M+H)+.

1. temperatureThe solution was then warmed to −40° C.
2. temperaturemaintained there for 1 h
3. temperaturethe solution warmed to 0° C
4. waitAfter 1 h
5. customthe ice bath was removed
6. temperatureto warm to rt
7. customThe solution was quenched with MeOH
8. additiondiluted with brine (200 mL)
9. extractionextracted with EtOAc (300 mL)
10. customThe organic layer was removed
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude material was purified

ORD record

ord-ba9d00f7054c4a2980bc7d724ce8db86

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062070B2