Lithium Hexamethyldisilazide → 1,1-Dimethylethyl N-[4-(3-amino-1,2,4-thiadiazol-5-yl)phenyl]carbamate

To a solution of tert-butyl 4-(3-bromo-1,2,4-thiadiazol-5-yl)phenylcarbamate (3.22 g, 9.04 mmol) in THF (35 mL) at 0° C. was added LiHMDS (1 M in PhMe, 23 mL, 23.0 mmol). The reaction mixture was warmed to room temperature and stirred for 1.5 h. Water (20 mL) was added and the mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water, saturated NH4Cl, and EtOAc. The aqueous phase was extracted with EtOAc (2×), and the combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, and concentrated. The concentrate was dissolved in 10% MeOH in DCM (200 mL), filtered through a pad of silica (2 cm), and diluted with hexanes (150 mL). The precipitate that formed was collected by filtration, washed with hexanes, and dried under high vacuum to give tert-butyl 4-(3-amino-1,2,4-thiadiazol-5-yl)phenylcarbamate.

1. stirringthe mixture was stirred at room temperature for 2 h
2. extractionThe aqueous phase was extracted with EtOAc (2×)
3. washthe combined organic extracts were washed with brine (1×)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. dissolutionThe concentrate was dissolved in 10% MeOH in DCM (200 mL)
8. filtrationfiltered through a pad of silica (2 cm)
9. additiondiluted with hexanes (150 mL)
10. customThe precipitate that formed
11. filtrationwas collected by filtration
12. washwashed with hexanes
13. customdried under high vacuum

ORD record

ord-eeb09a77e0a640fa851afe659f4dd59d

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324396B2