Water → 5-bromo-N-(4,4-dimethylcyclohexyl)-2,3-dihydro-1H-inden-1-amine

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Reaction Steps

To a slurry of 5-bromo-1-indanone (0.449 g; 2.13 mmol) and 4,4-dimethylcyclohexanamine (2.24 mmol; Note 1) under N2 was added Ti(OiPr)4 (0.94 mL; 3.2 mmol) via syringe. The mixture was stirred 16 h at room temperature, a solution of NaBH3CN (0.134 g; 2.13 mmol) in EtOH (5 mL) was added and stirring continued an additional 4 h. Water was added and the whole was filtered through a pad of Celite (washed 2×EtOH, 2×THF). Combine filtrate and washings were concentrated in vacuo, the residue was taken up in CH2Cl2 and stirred under 1N NaOH for 1 h. Layers were separated, the aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in MeOH/THF/HOAc (15/3/0.3 mL respectively), NaBH3CN (0.134 g; 2.13 mmol) was added and the mixture was stirred at room temperature overnight. After 17 h the mixture was concentrated in vacuo, partitioned between CH2Cl2/1N NaOH and the layers were separated. The aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes; Note 2), affording the title compound as a pale yellow syrup. LC/MS (method A) tR 1.79 min; m/z 322, 324 (M+H, Br isotopes).

Provenance & Evidence