Water → HCID 67542367, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of the title C compound, (3R,4R)-4-biphenyl-3-yl-3-hydroxy-piperidine-1-carboxylic acid ethyl ester (150 mg, 0.45 mmol) and sodium hydride (60% dispersion in mineral oil, 30 mg, 0.68 mmol) in 10 mL of dry DMF is stirred for 10 min at 60° C. under argon. After cooling to room temperature, 1-bromomethyl-2-(3-methoxy-propoxy)-4-methyl-benzene (252 mg, 0.9 mmol) is added and the mixture further stirred for 3 h at 60° C. After addition of H2O, the aqueous layer is extracted twice with ethyl acetate and the combined organic extracts are dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified by preparative HPLC (Macherey-Nagel 250/4 nucleosil 100-10 C18 column, 20:80 CH3CN+0.1% TFA over 11 min, then 100% CH3CN+0.1% TFA for 5.5 min, 40 mL/min). To the combined fractions containing the desired product is added 1M aqueous sodium carbonate solution and the acetonitrile is removed under reduced pressure. The resulting aqueous suspension is extracted twice with ethyl acetate. The combined organic layers are dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the title compound. MS 535.2 [M+18]; Rt (HPLC, Nucleosil C18, 10:90-100:0 CH3CN/H2O+0.1% TFA within 5 min, then 100% CH3CN+0.1% TFA): 7.29 min.

Provenance & Evidence