Sodium bis(trimethylsilyl)amide → tert-Butyl 5-fluoro-2-oxo-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxylate

To a stirred solution of 5-fluoro-1,3-dihydro-2H-indol-2-one (1.80 g, 11.9 mmol) in tetrahydrofuran (30 mL) was added dropwise a 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (35.7 mL, 35.7 mmol) at −78° C. for 15 min and the mixture was stirred for 1.5 h at the same temperature. To the mixture was added dropwise a solution of tert-butyl bis(2-chloroethyl)carbamate (2.88 g, 11.9 mmol) in tetrahydrofuran (10 mL) at −78° C., then this resulting mixture was slowly warmed up to room temperature and stirred for 19 h at the same temperature. The reaction mixture was quenched by the addition of ammonium chloride aqueous solution, and concentrated to give a brown residue. The crude material was partitioned between ethyl acetate and water, and then the organic layer washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (100 g) eluting with hexane/acetone (3/1) to afford 356 mg (15%) of the title compound as a slight brown syrup:

1. stirringstirred for 19 h at the same temperature
2. customThe reaction mixture was quenched by the addition of ammonium chloride aqueous solution
3. concentrationconcentrated
4. customto give a brown residue
5. customThe crude material was partitioned between ethyl acetate and water
6. washthe organic layer washed with brine
7. dry with materialdried over sodium sulfate
8. customevaporated
9. customThe residue was purified by column chromatography on silica gel (100 g)
10. washeluting with hexane/acetone (3/1)

ORD record

ord-8593bfc2dc644d4da2272c83d606233d

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07354925B2