Acetic Acid → 4-{[(2,4-Dichloro-thiazol-5-yl)methyl]-isobutyl-amino}-piperidine-1-carboxylic acid t-butyl ester

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Reaction Steps

To a solution of 4-(isobutylamino)-piperidine-1-carboxylic acid tert-butyl ester (797 mg, 2.28 mmol, 1 eq.) and 2,4-dichloro-5-thiazolecarboxaldehyde (500 mg, 2.75 mmol, 1.2 eq) in anhydrous dimethylformamide (10 ml), is added glacial acetic acid (130 uL, 2.28 mmol, 1 eq.) and NaBH(OAc)3 (677 mg, 3.19 mmol, 1.4 eq.). The reaction mixture is stirred at room temperature for 3 days and then water and ethyl acetate are added. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organics are washed with water, then dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue is purified on silica gel with 0 to 25% THF in hexanes to give 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-isobutyl-amino}-piperidine-1-carboxylic acid t-butyl ester (303 mg, 31%): m/z=422 (M+1); 1H NMR (250 MHz, CDCl3): δ=4.35 (2H, brd), 3.87 (2H, s), 2.80 (3H, m), 2.42 (2H,d), 1.86 (3H, m), 1.61 (11H, m), 1.06 (6H, d).

Provenance & Evidence