Sodium hydride → Tert-butyl 3-(3-methyl-4-nitrophenoxy)azetidine-1-carboxylate

In a dry flask, N-Boc-3-hydroxy-azetidine (9.8 g, 57 mmol) was dissolved in 200 mL of dry THF. The solution was cooled with an ice-water bath and sodium hydride (2.0 g, 83.mmol) was added in several portions. The suspension was stirred for an additional 0.5 hours, then 7.9 g of 2-nitro-5-fluorotoluene (7.9 g, 51 mmol) in 100 mL of dry THF was added dropwise. The solution was stirred overnight at room temperature. The THF was removed under vacuum and the residue was partitioned between ethyl acetate and water (100 mL each). The organic layer was collected and the aqueous layer was subsequently extracted twice with ethyl acetate. The combined organic layers were washed with 1 N HCl, water, saturated sodium bicarbonate and brine (50 mL each). The organic layer was dried over anhydrous sodium sulfate, concentrated. The residue was purified by silica gel column (EtOAc/Hexanes 1:19→1:4 gradient) to give 12.0 g (43 mmol, 84% yield) of the title compound, which was used directly in the next step. MS: 309 (M++1).

1. temperatureThe solution was cooled with an ice-water bath
2. stirringThe solution was stirred overnight at room temperature
3. customThe THF was removed under vacuum
4. customthe residue was partitioned between ethyl acetate and water (100 mL each)
5. customThe organic layer was collected
6. extractionthe aqueous layer was subsequently extracted twice with ethyl acetate
7. washThe combined organic layers were washed with 1 N HCl, water, saturated sodium bicarbonate and brine (50 mL each)
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. concentrationconcentrated
10. customThe residue was purified by silica gel column (EtOAc/Hexanes 1:19→1:4 gradient)

ORD-Eintrag

ord-e1434cd0a0eb4cb0b6404127ad9d73e6

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08088767B2