Ethyl bromoacetate → tert-Butyl (2S,4S)-2-[(2-ethoxy-2-oxoethoxy)methyl]-4-{[(1-isopropyl-1H-indazol-3-yl)carbonyl]amino}pyrrolidine-1-carboxylate

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Reaction Steps

To a stirred solution of tert-butyl (2S,4S)-2-(hydroxymethyl)-4-{[(1-isopropyl-1H-indazol-3-yl) carbonyl]amino}pyrrolidine-1-carboxylate (358 mg, 0.89 mmol, step 2 of Example 7) in tetrahydrofuran (7 mL) was added sodium hydride (60% dispersion in mineral oil, 90 mg, 2.2 mmol) at 0° C. Then to the solution was added 18-crown-6 (164 mg, 0.45 mmol) and a solution of ethyl bromoacetate (446 mg, 2.67 mmol) in tetrahydrofuran (5 mL) at 0° C. It was stirred overnight rising to room temperature. The resulting mixture was quenched by addition of water and it was extracted with ethyl acetate (10 mL×3). The organic layer was washed with brine, dried over sodium sulfate and concentrated. The resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (2:1 to 1:1) to give 310 mg (71%) of the title compound as a colorless oil.

Provenance & Evidence