2-(oxolan-2-yl)acetaldehyde

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:

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

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

Procedure: The solution of 2-Acetyl-4-bromophenol (1.754 g, 8.16 mmol), 2-(tetrahydrofuran-2-yl)acetaldehyde (2.1 g) and purrolidine (0.4 mL) in MeOH was heated to reflux for 2 h. The reaction mixture was cool down to room temperature and evaporated. The residue was dissolved in EA, washed with 1 M HCl, 1 M NaOH (2×50 mL), brine (100 mL) successively, then, dried over anhydrous Na2SO4, and filtered, and concentrated. The residue was purified by flash chromatography on silica gel eluting with EA in hexane (0-20%) to give 6-bromo-2-((tetrahydrofuran-2-yl) methyl)chroman-4-one (464 mg); MS ESI +ve m/z 311 (M+H)+. to reflux for 2 h evaporated The residue was dissolved in EA washed with 1 M HCl, 1 M NaOH (2×50 mL), brine (100 mL) successively dried over anhydrous Na2SO4 filtered concentrated The residue was purified by flash chromatography on silica gel eluting with EA in hexane (0-20%)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine (6.16 g, 24 mmol) in dry tetrahydrofuran (150 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (22.5 mL, 36 mmol) to a 0° C. solution of diisopropylamine (5.4 mL, 38 mmol) in dry tetrahydrofuran (20 mL)] dropwise. The mixture was stirred at −78° C. for 15 min and then treated with (tetrahydro-furan-2-yl)-acetaldehyde (4.9 g, 43 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×150 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 30% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-furan-2-yl)-ethanol as a colorless oil (0.9 g, 31%): LC/MS m/e calcd for C19H20N2O4S [M+H]+ 373.45, observed 373.3. prepared The resulting mixture was stirred at −78° C. for 1 h quenched with brine The mixture was extracted with ethyl acetate (2×150 mL) washed with brine dried over anhydrous sodium sulfate concentrated in vacuo Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 30% ethyl acetate/hexanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 10, 6 g, 20.8 mmol) in dry tetrahydrofuran (40 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (19.5 mL, 31.2 mmol) to a 0° C. solution of diisopropylamine (4.7 mL, 32.8 mmol) in dry tetrahydrofuran (20 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with (tetrahydro-furan-2-yl)-acetaldehyde (3.5 g, 30.7 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×200 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 25% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-furan-2-yl)-ethanol (2.5 g, 30%) as a white solid: LC/MS m/e calcd for C21H22N2O5S [M+H]+ 403.47, observed 403.2. prepared The resulting mixture was stirred at −78° C. for 1 h quenched with brine The mixture was extracted with ethyl acetate (2×200 mL) washed with brine dried over anhydrous sodium sulfate concentrated in vacuo Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 25% ethyl acetate/hexanes)

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

Procedure: The solution of 2-Acetyl-4-bromophenol (1.754 g, 8.16 mmol), 2-(tetrahydrofuran-2-yl)acetaldehyde (2.1 g) and purrolidine (0.4 mL) in MeOH was heated to reflux for 2 h. The reaction mixture was cool down to room temperature and evaporated. The residue was dissolved in EA, washed with 1 M HCl, 1 M NaOH (2×50 mL), brine (100 mL) successively, then, dried over anhydrous Na2SO4, and filtered, and concentrated. The residue was purified by flash chromatography on silica gel eluting with EA in hexane (0-20%) to give 6-bromo-2-((tetrahydrofuran-2-yl)methyl)chroman-4-one (464 mg); MS ESI+ve m/z 311 (M+H)+. to reflux for 2 h evaporated The residue was dissolved in EA washed with 1 M HCl, 1 M NaOH (2×50 mL), brine (100 mL) successively dried over anhydrous Na2SO4 filtered concentrated The residue was purified by flash chromatography on silica gel eluting with EA in hexane (0-20%)

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