Triethylamine → Metanephrine

Temperature

100 °C

A solution of I-109 (1.3 mmol, 0.70 g) in dioxane (14 mL) is added to three Endeavor reactors. [1,1′-Bis(diphenylphosphino)ferrocene]dichloro palladium(II) dichloromethane adduct (0.07 mmol, 0.05 g), triethylamine (2.6 mmol, 0.36 mL) and water (0.15 mL) are added to each reactor. The reaction mixture is stirred at 100° C. under CO atmosphere at 100 psi for 15 h to yield I-145 (0.47 g, 72%). I-145 (0.1 mmol, 0.05 g) and pyrrolidine (0.25 mmol, 0.020 mL) in DMF (2 mL) is treated with TBTU (0.05 g, 0.16 mmol) followed by Hunig's base (0.20 mL, 1.15 mmol) and the mixture is stirred at 40° C. for 2 h. Water (10 mL) is added and the organics are extracted with DCM (2×5 mL). Organics are combined and concentrated to give I-146 that is dissolved in THF (1 mL), methanol (1 mL) and aqueous 5M NaOH (0.25 mL) and heated at 60° C. for 5 min and then stirred at ambient temperature for 5 min. The mixture is concentrated and diluted with DCM, then acidified to pH=5-6 with 1N HCl. The mixture is concentrated in vacuo and purified by HPLC to give the title compound (0.010 g, 57%).

1. customto yield I-145 (0.47 g, 72%)
2. stirringthe mixture is stirred at 40° C. for 2 h
3. extractionthe organics are extracted with DCM (2×5 mL)
4. concentrationconcentrated

ORD record

ord-92298ad8a67649c4b9a22ebf0c82d271

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815857B2