4.3. Preparation of 4-(prop-2-ynyloxy) benzoic acid (15b)
The methyl ester 14a (613 mg, 3.0 mmol) was dissolved in THF (20 mL) at room
temperature and then treated with KOH solution (840 mg, 15 mmol in 15 mL methanol).
After the reaction mixture was stirred at room temperature overnight, solvent was evaporated
under vacuum. Then, the concentrated sample was acidified with aqueous HCl (6.0 M) and
extracted with ethyl acetate (3×15 mL). The combined organic layers were washed with brine
and dried over Na2SO4. After evaporation of the solvent, the product was obtained as a white
crystalline solid with 78% yield.
4.4. Typical procedure for the preparation of 1,2,3-triazole derivatives 2c-16c
Synthesis of 7-((1-((5-Hydroxy-4-oxo-4H-pyran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)-
2H-chromen-2-one (2c). Firstly, the required catalyst copper (I) was prepared by adding
copper (II) sulfate pentahydrate (CuSO4.5H2O, 30 mg, 10 mol%) to the solution of sodium
ascorbate (95.1 mg, 40 mol%) in deoxygenated water (3 mL). After dissolving of
CuSO4.5H2O and alteration the color of solution to green, it was ready for next step. The
propargyl derivative 7-(prop-2-yn-1-yloxy)-2H-chromen-2-one (2b, 1.0 mmol) and azide 1b
(1.0 mmol) were dissolved in a mixed solvents THF (10 mL) and tert-butyl alcohol (1 mL).
Then, the pre-prepared solution of Cu (I) was added dropwise to the clickable reactants
solution and the mixture was stirred at r.t. for 1h. After confirming the completion of the
reaction by TLC, the solvents were removed by evaporation under reduced pressure. The
obtained residue was mixed with water (30 mL, containing 10% EDTA disodium salt) and
extracted with ethyl acetate (3×15 mL). The collected organic phases were washed with brine
and dried (Na2SO4). After solvent evaporation under reduced pressure, the product was
triturated with a small amount of cold acetone and recrystallized from methanol to give pure
1
final compound 2c. White solid; yield 83%; m.p. 205-207 °C; H NMR (500 MHz, DMSO-
d6) δ: 9.29 (br s, 1H, OH), 8.39 (s, 1H, H-6 pyran), 8.05 (s, 1H, triazole), 7.99 (d, 1H, J = 9.5
Hz, H-4 coumarin), 7.64 (d, 1H, J = 8.5 Hz, H-5 coumarin), 7.16 (d, 1H, J = 1.5 Hz, H-8
coumarin), 7.02 (dd, 1H, J = 8.5 and 1.5 Hz, H-6 coumarin), 6.41 (s, 1H, H-3 pyran), 6.30 (d,
13
1H, J = 9.5 Hz, H-3 coumarin), 5.63 (s, 2H, OCH2), 5.29 (s, 2H, NCH2). C NMR (125
MHz, DMSO-d6) δ: 174.07, 161.52, 160.97, 160.70, 155.76, 146.51, 144.72, 142.92, 140.49,
129.99, 126.20, 113.57, 113.36, 113.19, 113.11, 102.06, 62.00, 50.48. MS (m/z, %): 367 (M+,
6), 178 (20), 162 (18), 134 (62), 105 (41), 89 (25), 67 (63), 41 (100). Anal. Calcd for
C18H13N3O6: C, 58.86; H, 3.57; N, 11.44. Found: C, 58.82; H, 3.56; N, 11.53.
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