Triphenylphosphine → HCID 67534128, compound

Participants

Reaction Conditions

Reaction Steps

The product from Example 165E (0.4 g), 4-cyanophenylboronic acid(0.45 g, 2.5 eq), triphenylphosphine (65 mg, 0.2 eq), and bistriphenylphosphine palladium dichloride (87 mg, 0.1 eq) in isopropanol (8 mL) was treated with potassium phosphate (0.52 g, 2 eq) in 8 mL of water. The mixture was heated at 65° C. under nitrogen for 25 hours, allowed to cool to room temperature, and treated with H2O:NMP:MeSO3H (70:20:10, 10 mL). The mixture was extracted with toluene (2×10 mL) and the acidic aqueous phase was basified to pH 10 using 50% NaOH. The basified solution was extracted with methylene chloride (10 mL), washed with water (2×10 mL), and concentrated to a brown oil. The brown oil was dissolved in EtOAc (20 mL), washed with water (2×10 mL), and concentrated. The residue was purified by column chromatography (silica gel, 10:90 MeOH:CHCl3) to provide the title compound (0.37 g). MS m/z 347(M+H)+. The free base was dissolved in 5 mL of MeOH and added to L-tartaric acid (0.16 g, 1 eq) in 5 mL of MeOH. The mixture was concentrated to dryness, and crystallized from EtOAc/EtOH to give the tartrate salt (0.33 g). 1H NMR(DMSO-d6) δ 1.17 (doublet), 1.41-1.49(multiplet), 1.74-1.82(multiplet), 1.97-2.03(multiplet), 2.55-2.59(multiplet), 2.80 (multiplet), 3.12-3.37(multiplet), 4.11(singlet), 7.33 (singlet), 7.66 (doublet), 7.93(singlet), 8.02(doublet), 8.13(doublet).

Provenance & Evidence