Pivaloyl chloride → HCID 15984737, compound

Participants

Reaction Steps

To a stirred mixture of (3S,5R)-3-amino-5-{cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester (374 mg, 0.62 mmol), N-ethyldiisopropylamine (503 μl, 2.94 mmol) and 4-dimethylaminopyridine (31 mg) in CH2Cl2 (8 ml), pivaloylchloride (126 μl, 1.02 mmol) is added. After stirring for 14 h at RT, the mixture is diluted with CH2Cl2. The organic layer is washed with 1N HCl and saturated NaHCO3 solution, dried over Na2SO4 and evaporated in vacuo. The crude product is stirred with a solution of CH2Cl2/piperidine 4:1 (6 ml) for 1 h, the mixture is evaporated and the residue purified by preparative HPLC (YMC Pack Pro C18, 10-100% CH3CN+0.1% TFA/H2O+0.1% TFA, 20 min, flow 20 ml/min). The combined pure fractions are treated with K2CO3, CH3CN is removed in vacuo, and the residual aqueous layer is extracted three times with CH2Cl2. The combined organic layers are dried (Na2SO4) and evaporated to afford the title compound as a yellowish resin. MS: 469.4 [M+H]+; tR (HPLC, Nucleosil C18; 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 8 min, flow 1.5 ml/min): 5.03 min.

Provenance & Evidence