Sodium bis(trimethylsilyl)amide → (R)-tert-butyl 2-(1'-benzyl-2-oxospiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylate

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Reaction Steps

NaHMDS (5.0 mL, 5.0 mmol) was added into a solution of (R)-tert-butyl 2-(2-oxoindolin-4-yl)pyrrolidine-1-carboxylate (300 mg, 0.992 mmol) in THF (10 mL) at −78° C. The mixture was stirred for 20 minutes at that temperature. N-benzyl-2-chloro-N-(2-chloroethyl)ethanamine HCl salt (300 mg, 1.12 mmol) was added into the solution at −78° C. The reaction mixture was allowed to warm up to room temperature and was heated to reflux for 12 hours. The reaction was quenched by pouring the reaction mixture into water (10 mL) and was extracted with EtOAc (100 mL). The organic layer was washed with brine, dried with Na2SO4, filtered and concentrated. The residue was purified with flash chromatography to afford the product (R)-tert-butyl 2-(1′-benzyl-2-oxospiro[indoline-3,4′-piperidine]-4-yl)pyrrolidine-1-carboxylate (150 mg, 0.325 mmol, 32.8%) as a solid. 1H NMR (CDCl3, 400 MHz) δ 7.20-7.45 (m, 6H), 7.10 (t, 1H), 6.80 (d, 1H), 6.60-6.70 (m, 1H), 5.40-5.80 (m, 1H), 3.50-3.80 (m, 4H), 3.00-3.20 (m, 2H), 2.90-3.00 (m, 2H), 2.75-2.85 (m, 2H), 2.60-2.70 (m, 1H), 2.20-2.50 (m, 2H), 1.90-2.00 (m, 1H), 1.80-1.90 (m, 1H), 1.70-1.80 (m, 1H), 1.60-1.70 (m, 1H), 1.50-1.60 (m, 1H), 1.00-1.50 (m, 9H). MS (APCI+) [M+H]+ 462.

Provenance & Evidence