ethyl 6-hydroxy-1-benzofuran-2-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-hydroxy-benzofuran-2-carboxylic acid ethyl ester (2.0 g, 10 mmol) in MeCN (100 mL) added Cs2CO3 (6.3 g, 19 mmol) followed by 2-chloro-thiazolo[4,5-b]pyridine hydrochloride (2.0 g, 10 mmol) and the reaction mixture was stirred (rt, 12 h). The reaction mixture was treated with H2O (50 mL) and the solid was filtered to afford the title compound as a beige solid (2.3 g, 69%). MS (ESI): mass calcd. for C17H12N2O4S, 340.1; m/z found, 341.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.58 (dd, J=4.8, 1.6, 1H), 8.04 (dd, J=7.9, 1.6, 1H), 7.75-7.69 (m, 2H), 7.55 (d, J=0.8, 1H), 7.42 (dd, J=8.6, 2.1, 1H), 7.22 (dd, J=7.9, 4.8, 1H), 4.46 (q, J=7.1, 2H), 1.44 (t, J=7.1, 3H). the solid was filtered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 6-benzyloxy-benzofuran-2-carboxylic acid ethyl ester (8.1 g, 27 mmol) in EtOAc/EtOH (3/1, 130 mL) was added Pd/C (0.8 g). The reaction mixture was shaken in a Parr Shaker under H2 (50 psi, 12 h). The reaction mixture was filtered (Celite®), washed with EtOAC (400 mL) and EtOH (100 mL). The filtrate was concentrated and the resulting residue was purified by silica gel flash chromatography using EtOAc:hexanes (0-50%) to provide the title compound as colorless solid (3.9 g, 70%). MS (ESI): mass calcd. for C11H10O4, 206.1.0; m/z found, 207.1 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.50 (d, J=8.6, 1H), 7.46 (d, J=0.8, 1H), 7.25-7.23 (m, 1H), 6.90 (dd, J=8.5, 2.2, 1H), 6.12 (s, 1H), 4.57-4.30 (m, 2H), 1.49-1.31 (m, 3H). The reaction mixture was filtered (Celite®) washed with EtOAC (400 mL) and EtOH (100 mL) The filtrate was concentrated the resulting residue was purified by silica gel flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixed solution of 6-hydroxy-benzofuran-2-carboxylic acid ethyl ester (200 mg, 967 μmol) in tetrahydrofuran (4 mL) and N,N-dimethylformamide (4 mL) were added diphenylindonium iodine (395 mg, 967 μmol) and potassium t-butoxide (109 mg, 967 μmol) at 0° C., which was stirred at room temperature for 40 minutes under nitrogen atmosphere. After further stirring for 3 hours at 60° C., water was added to the reaction solution at room temperature followed by extraction with ethyl acetate, washing the organic layer with sat. NaCl, drying over anhydrous magnesium sulfate and filtering. The filtrate was concentrated under a reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1) to obtain the title compound (189 mg, 69%) as a colorless oil. After further stirring for 3 hours at 60° C. followed by extraction with ethyl acetate washing the organic layer with sat. NaCl drying over anhydrous magnesium sulfate filtering The filtrate was concentrated under a reduced pressure the residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixed solution of 6-hydroxy-benzofuran-2-carboxylic acid ethyl ester (250 mg, 1.21 mmol) in tetrahydrofuran (5 mL) and N,N-dimethylformamide (5 mL) were added sodium hydride (58 mg, 2.42 mmol) and 1-bromo-2-butyne (127 μL) at room temperature, which was stirred at room temperature for 1 hour. Water was added to the reaction solution followed by extraction with ethyl acetate. The organic layer was washed with water and sat. NaCl followed by drying over anhydrous magnesium sulfate and filtering. The filtrate was concentrated under a reduced pressure and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1) to obtain the title compound (254 mg, 81%) as a white solid. followed by extraction with ethyl acetate The organic layer was washed with water and sat. NaCl by drying over anhydrous magnesium sulfate filtering The filtrate was concentrated under a reduced pressure the residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1)