Ethyl Acetate → Methyl 5-amino-1-bromo-indan carboxylate

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Reaction Steps

Add N-bromosuccinimide (1.87 g, 10.5 mmol) to methyl 6-amino-indan-5-carboxylate (1.82 g, 9.53 mmol) (Example 49, Step 3) in acetic acid (9.3 mL). Stir the mixture at room temperature for 1 h. Pour the mixture into ice water and add ethyl acetate. Separate the layers and wash the organic phase with saturated NaHCO3 and brine and dry over sodium sulfate. Remove the solvent under reduced pressure. Purify with silica gel cartridge, eluting with hexanes/ethyl acetate to afford methyl 5-amino-1-bromo-indan carboxylate (2.45 g, 95%): MS (ES+): 271, 272 (M+H). Add methyl boronic acid (1.6 g, 26.7 mmol), cesium fluoride (4.6 g, 30.22 mmol) and 1-bis(diphenylphosphinoferrocene) palladium chloride (727 mg, 0.89 mmol) to methyl 5-amino-1-bromo-indan carboxylate (2.40 g, 8.89 mmol) in dioxane (60 ml), and stir at 90° C. for 12 h. Partition between water and ethyl acetate. Extract with more ethyl acetate and then combine the organic phases. Dry over sodium sulfate and remove the solvent under reduced pressure. Purify with silica gel cartridge, eluting with hexanes/ethyl acetate to afford the titled compound (1.73 g, 95%). MS (ES+): 206 (M+H).

Provenance & Evidence