Hydrogen Bromide → 2-Bromo-1-(4-(dibenzylamino)-2-methylcyclopentyl)ethanone

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Reaction Steps

Oxalyl chloride (4.37 mL, 49.9 mmol) was slowly added to a solution of 4-(dibenzylamino)-2-methylcyclopentanecarboxylic acid (7.34 g, 22.7 mmol) in DCM (100 mL), (note: mild gas evolution) followed by a dropwise addition of DMF (0.26 mL, 3.41 mmol). The mixture was stirred at ambient temperature for about 14 h. The solvent was removed under reduced pressure to yield a beige amorphous solid, which was dissolved in THF and MeCN (1:1, 100 mL). The resulting solution was added to a solution of trimethylsilyldiazomethane (2 M in Et2O, 39.7 mL, 79 mmol) in THF and MeCN (1:1, 100 mL) at about 0° C. The resulting mixture was stirred at about 0° C. for about 3 h and then was quenched by a dropwise addition of HBr (48% aqueous, 25 mL, 221 mmol). The resulting mixture was neutralized by a dropwise addition of saturated aqueous NaHCO3 (300 mL) and the layers were separated. The organic layer was dried over anhydrous MgSO4 and concd under reduced pressure. The residue was purified by silica gel chromatography eluting with 5% to 45% of EtOAc in heptane to yield 2-bromo-1-(4-(dibenzylamino)-2-methylcyclopentyl)ethanone (6.3 g, 69%) as a yellow oil: LC/MS (Table 1, Method a) Rt=2.90 min; MS m/z 400, 402 (M+H)+.

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