Ammonium Chloride → tert-butyl 7-hydroxy-6-oxohexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Temperature

-78 °C

To a solution of the product from Example 205A (0.20 g, 0.832 mmol) in anhydrous tetrahydrofuran (6 mL) at −78° C. under N2 was added a 1 M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (1.25 mL, 1.25 mmol). The resulting mixture was stirred at −78° C. for 20 minutes, and then a solution of 3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (0.326 g, 1.248 mmol) in anhydrous tetrahydrofuran (3 mL) was added dropwise. The mixture was stirred at −78° C. for 20 minutes, and then it was warmed to −40° C. and stirred for an additional 2 hours. A solution of NH4Cl (10% in water, 2 mL) was added, the mixture was allowed to warm to room temperature, and the mixture was partitioned between water and ethyl acetate (5×). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane to give the title compound (89 mg, 42%).

1. stirringThe mixture was stirred at −78° C. for 20 minutes
2. temperatureit was warmed to −40° C.
3. stirringstirred for an additional 2 hours
4. temperatureto warm to room temperature
5. customthe mixture was partitioned between water and ethyl acetate (5×)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane

ORD record

ord-61adc6894b8247c3adad5092b13ad053

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669255B2