Lithium hexamethyldisilazane → (S)-2-(4-Bromo-2-fluorophenylamino)-N-(2-(tert-butyldimethylsilyloxy)propoxy)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide

To a solution of methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.050 g, 0.14 mmol) and (S)—O-(2-(tert-butyldimethylsilyloxy)propyl)hydroxylamine (0.072 g, 0.35 mmol) in THF (1.50 mL) at 0° C. was slowly added lithium bis(trimethylsilyl)amide (0.70 ml, 0.70 mmol). After addition, the reaction mixture was stirred for 1 hour at room temperature and then quenched by with saturated NaHCO3. The reaction mixture was partitioned between EtOAc and sat NaCl. The layers were separated and the aqueous layer was back-extracted with EtOAc (1×). The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure to yield a crude brown solid that was used without further purification in the next step.

1. customat 0° C.
2. additionAfter addition
3. customquenched by with saturated NaHCO3
4. customThe reaction mixture was partitioned between EtOAc
5. customThe layers were separated
6. extractionthe aqueous layer was back-extracted with EtOAc (1×)
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto yield a crude brown solid that
11. customwas used without further purification in the next step

ORD record

ord-b8c48c3579774890b4ee9d4299466d48

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101639B2