Dimethylformamide → 4-(Dibenzylamino)-2-methylcyclopentanecarbonyl chloride

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Reaction Steps

To a solution of 4-(dibenzylamino)-2-methylcyclopentanecarboxylic acid (7.34 g, 22.7 mmol, Preparation #TT.1) in DCM (100 mL), oxalyl chloride (4.37 mL, 49.9 mmol) was slowly added followed by a dropwise addition of DMF (0.26 mL, 3.4 mmol). The mixture was stirred at ambient temperature for about 14 h and the solvent was removed under reduced pressure to yield 4-(dibenzylamino)-2-methylcyclopentanecarbonyl chloride as a beige solid. The solid was dissolved in THF and MeCN (1:1, 100 mL) and added to a solution of trimethylsilyldiazomethane (2 M in Et2O, 39.7 mL, 79.4 mmol) in 1:1 mixture of THF and MeCN (100 mL) at about 0° C. The resulting mixture was stirred at about 0° C. for about 3 h and then was quenched by dropwise addition of 48% aqueous HBr (25 mL, 221 mmol). The resulting mixture was neutralized by dropwise addition of saturated aqueous NaHCO3 (300 mL) and the layers were separated. The organic layer was dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 5-45% 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 (1:1) (M+H)+.

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