Hydrochloric Acid → HCID 53234306, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-ol (Example 9, 0.1 g, 0.327 mmol) in acetonitrile (2 mL) was added potassium carbonate (0.100 g, 0.720 mmol) and (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (0.094 g, 0.327 mmol) at room temperature. The heterogeneous reaction mixture was heated at 120° C. in a microwave reactor for 1 h. Next, 2 mL of methanol was added followed by additional (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (100 mg). The contents were heated in the microwave reactor at 120° C. for 1 h. To the reaction mixture was added 1.0 mL of 2.5 M hydrochloric acid in ethanol at room temperature. The heterogeneous reaction mixture was stirred at room temperature for 1.5 h and concentrated under reduced pressure. Methanol (3 mL) was added followed by 3 drops of water and the contents were filtered. The pale yellow filtrate was subjected to Prep. HPLC (PHENOMENEX® Luna Axia 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA). Fractions corresponding to the desired product were isolated and concentrated to yield (R)-3-(3-(4-propylphenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yloxy)propane-1,2-diol (0.016 g, 0.042 mmol, 13% yield) as a white solid. The compound had an HPLC retention time=3.73 min (condition C); LC/MS M+1=380.1; 1H NMR (400 MHz, CDCl3) δ ppm 7.93 (d, J=8.53 Hz, 1H) 7.69 (d, J=8.28 Hz, 2H) 7.31 (d, J=8.28 Hz, 2H) 6.85-6.92 (m, 2H) 4.08-4.15 (m, 3H) 3.74-3.91 (m, 2H) 2.96-3.05 (m, 4H) 2.55-2.68 (m, 3H) 1.97 (t, J=5.90 Hz, 1H) 1.68 (sxt, J=7.43 Hz, 2H) 0.97 (t, 3H).

Provenance & Evidence