1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ammonium Hydroxide

Participants

Reaction Steps

To a flask equipped with a magnetic stir bar and addition funnel under argon atmosphere was added (S)-5-bromo-indan-2-carboxylic acid (383 mg, 1.59 mmol, obtained by following the procedures of patent WO96/23760), EDCI (358 mg, 1.87 mmol), HOBT (291 mg, 2.16 mmol) and CH2Cl2 (3 mL). This solution was stirred at rt for 5 min. To this solution was then added dropwise a solution of (3R,4R)-1-(3-methoxy-piperidin-4-yl)-2,5-dimethyl-1H-benzoimidazole (375 mg, 1.44 mmol) in CH2Cl2 (2 mL). The reaction was then stirred at rt overnight for 20 hours. The reaction was quenched by the addition of water (10 mL) and extracted three times with CH2Cl2. The organic extracts were combined and dried over Na2SO4, filtered and concentrated in vacuo. Flash chromatography (Biotage 12M column, 3% CH3OH in ethyl acetate plus 1% NH4OH) afforded the desired product which was contaminated with some HOBT. The product foam was then dissolved in CH2Cl2 and washed with a saturated NaHCO3 solution. The organic was dried over Na2SO4, filtered and concentrated under reduced pressure to yield ((S)-5-bromo-indan-2-yl)-[(3R,4R)-4-(2,5-dimethyl-benzoimidazol-1-yl)-3-methoxy-piperidin-1-yl]-methanone (579 mg, 83%) as a light yellow foam. HR-ES(+) m/e calcd for C25H28N3O2Br (M+H)+ 482.1438, found 482.1436.

Provenance & Evidence