Cyclohexylacetone → 3-[(4-Cyclohexylmethyl-thiazol-2-yl)-(5-ethyl-thiophen-2-ylmethyl)-amino]-propionic acid

Participants

Reaction Steps

Cyclohexylacetone (300 mg, 2.14 mmol) in MeOH (5 mL) was treated with pyrrolidone hydrotribromide (1.3 g, 4.28 mmol) and the reaction was stirred at RT overnight. To the resulting solution of crude alpha-bromoketone in MeOH (without workup) was directly added solid sodium bicarbonate to neutralize the acid formed in the bromination step. To this neutralized bromoketone mixture was added 3-[1-(5-ethyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester (150 mg) in THF (2 mL) and the reaction was stirred for 1 h at RT. The solvent was removed at reduced pressure and the residue was dissolved in water and ethyl acetate. The aq portion was extracted two times with EtOAc, and the combined organic portion was washed with brine and then dried over sodium sulfate. Solvent removal under reduced pressure gave the crude product which was partially purified by silica gel chromatography (eluent: 10:1 hexanes:EtOAc) to give the aminothiazole derivative (300 mg).

Provenance & Evidence