Optimelt automated melting point system

Naltrexone (NTX) was obtained as a free base through the NIDA Drug Supply Program. Other reagents were purchased from commercial vendors (such as Sigma-Aldrich and Aldlab Chemicals) and used without further purification. Flash column chromatography was performed with silica gel columns (230-400 mesh, Merck). ¹H (400 MHz) and ¹³C (100 MHz) nuclear magnetic resonance (NMR) spectra were recorded with tetramethylsilane as the internal standard on a Bruker Ultrashield 400 Plus spectrometer. High resolution mass spectroscopy (HRMS) was performed on an Applied Bio Systems 3200 Q trap with a turbo V source for TurbolonSpray. HPLC analysis was done with a Varian ProStar 210 system on Microsorb-MV 100-5 C8/C18 column (250 mm × 4.6 mm) at 254 nm, eluting with acetonitrile/water (0.1% TFA) (85/15) at 1 mL/min over 30 min. Melting points were determined using OptiMelt automated melting point system (Fisher Scientific).

Reagents were purchased from either Sigma-Aldrich or Alfa Aesar. TLC analyses were carried out on the Analtech Uniplate F254 plates. Chromatographic purification was conducted on silica gel column (230–400 mesh, Merck). ¹H (400 MHz) and ¹³C (100 MHz) nuclear magnetic resonance (NMR) spectra were recorded at ambient temperature with tetramethylsilane as the internal standard on a Varian Mercury 400 MHz NMR spectrometer.
Melting points were recorded with OptiMelt automated melting point system (Fisher Scientific). IR spectra were obtained with Nicolet iS10 instrument (Thermo Scientific). Applied Bio Systems 3200 Q trap with a turbo V source for TurbolonSpray was used for MS analysis. HPLC analysis was performed by a Varian ProStar 210 system on Agilent Microsorb-MV 100–5 C18 (250 mm × 4.6 mm) at 210 nm with water/acetonitrile (25/75, 30/70 or 35/65, 0.01% TFA in water) at 0.8 mL/min over 30 min. The purity of the third generation NAP derivatives was determined by above analytical methods, and their purity was identified as ≥95%.