Acetic Acid → 1-[3-(Ethyloxy)-4-nitrophenyl]-4-(4-piperidinyl)piperazine

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Reaction Steps

To a stirred solution of 1-[3-(ethyloxy)-4-nitrophenyl]piperazine (Example 143, step A) (0.53 g, 2.1 mmol) and 1-BOC-4-piperidone (2.1 g, 10.6 mmol) in DCE (21 mL) was added HOAc (0.25 g, 4.2 mmol) followed by addition of sodium triacetoxyborohydride (2.2 g, 10.6 mmol). The reaction was stirred under N2 at rt for 3 h. The reaction was quenched with aqueous (saturated) NaHCO3 and extracted with DCM (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. The desired fractions were concentrated under vacuum. The residue was dissolved and stirred in a 20% solution of TFA/DCM (50 mL) for approximately 2 h at rt. The mixture was concentrated under vacuum. The residue was dissolved in DCM and neutralized with aqueous (saturated) NaHCO3. The aqueous layer was extracted with DCM (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography. The desired fractions were concentrated under vacuum to give the title compound of step A (560 mg, 1.68 mmol, 79%) as a yellow solid. MS (ESI): 335 [M+H]+.

Provenance & Evidence