2-(3,4-dihydro-2H-chromen-4-yl)acetaldehyde

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanal (875 mg, 5 mmol) and 4-(2-benzofurancarboxamido)piperidine hydrochloride (1.4 g, 5 mmol)under a nitrogen atmosphere, borane/pyridine complex (0.5 ml, excess) was added. The reaction was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether. The diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (520 mg). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ammonium hydroxide; 85/14/1) to afford an oil (260 mg) which was crystallized from diethyl ether to afford the title compound (150 mg, 7%), mp=146°-8°. Anal: C25H28N2O3 0.5 H2O, Calc. C, 72.62; H, 7.07; N, 6.77; Found C,72.40; H, 6.94; N, 6.83. evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid The acidic solution was extracted with diethyl ether The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide The ethyl acetate layer was washed with distilled water dried (Na2SO4) filtered evaporated

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanal (875 mg, 5 mmol) and 4-(2-benzofurancarboxamido)piperidine hydrochloride (1.4 g, 5 mmol)under a nitrogen atmosphere, borane/pyridine complex (0.5 ml, excess) was added. The reaction was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether. The diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (520 mg). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ammonium hydroxide; 85/14/1) to afford an oil (260 mg) which was crystallized from diethyl ether to afford the title compound (150 mg, 7%), mp=146°-8°. Anal: C25H28N2O3 0.5 H2O, Calc. C, 72.62; H, 7.07; N, 6.77; Found C,72.40; H, 6.94; N, 6.83. evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid The acidic solution was extracted with diethyl ether The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide The ethyl acetate layer was washed with distilled water dried (Na2SO4) filtered evaporated

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl]ethanal (2.50 g, 14.28 mmol) and 4-acetamidopiperidine AcOH (2.88 g, 14.28 mmol) (preparation described in U.S. Pat. No. 5,028,616) in ethanol (80 ml) under a nitrogen atmosphere, borane/pyridine complex (1.5 ml, 15 mmol) was added. The reaction mixture was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether and the diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of a 50% sodium hydroxide solution. The basic solution (>pH 12) was extracted with ethyl acetate. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (3.56 g). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ ammonium hydroxide; 85/14/1) to afford an oil (2.56 g) which was crystallized from diethyl ether to afford the title compound (2.40 g, 56%) mp=126°-8°. Anal: C18H26N2O2Calc.: C 71.49; H 8.67; N 9.26; Found C 71.46; H 8.84; N 9.26. evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid The acidic solution was extracted with diethyl ether The acidic aqueous layer was basified by dropwise addition of a 50% sodium hydroxide solution The basic solution (>pH 12) was extracted with ethyl acetate The ethyl acetate layer was washed with distilled water dried (Na2SO4) filtered evaporated

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanol (1.45g, 8 mmol), N-methylmorpholine-N-oxide (1.41 g, 12 mmol) and 4 A molecular sieves (4.0 g) in methylene chloride (20 ml), tetrapropylammonium perruthenate (0.140 g, 0.4 mmol) was added. The reaction mixture was stirred at room temperature for 15 min., diluted with an equal volume of ethyl acetate (20 ml) and flash filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1). Concentration of the filtrate in vacuo afforded the title compound as an oily gum (0.92 g, 64%). NMR (300 MHz/CDCl3) 9.87 (1 H, s). filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1)

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanol (1.45g, 8 mmol), N-methylmorpholine-N-oxide (1.41 g, 12 mmol) and 4 A molecular sieves (4.0 g) in methylene chloride (20 ml), tetrapropylammonium perruthenate (0.140 g, 0.4 mmol) was added. The reaction mixture was stirred at room temperature for 15 min., diluted with an equal volume of ethyl acetate (20 ml) and flash filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1). Concentration of the filtrate in vacuo afforded the title compound as an oily gum (0.92 g, 64%). NMR (300 MHz/CDCl3) 9.87 (1 H, s). filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1)

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanal (875 mg, 5 mmol) and 4-(2-benzofurancarboxamido) piperidine hydrochloride (1.4 g, 5 mmol) under a nitrogen atmosphere, borane/pyridine complex (0.5 ml, excess) was added. The reaction was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether. The diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (520 mg). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ammonium hydroxide; 85/14/1) to afford an oil (260 mg) which was crystallized from diethyl ether to afford the title compound (150 mg, 7%), mp=146-8°. Anal: C25H28N2O3 0.5 H2O, Calc. C, 72.62; H, 7.07; N, 6.77; Found C,72.40; H, 6.94; N, 6.83. evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid The acidic solution was extracted with diethyl ether The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide The ethyl acetate layer was washed with distilled water dried (Na2SO4) filtered evaporated

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl]ethanal (2.50 g, 14.28 mmol) and 4-acetamidopiperidine AcOH (2.88 g, 14.28 mmol) (preparation described in U.S. Pat. No. 5,028,616) in ethanol (80 ml) under a nitrogen atmosphere, borane/pyridine complex (1.5 ml, 15 mmol) was added. The reaction mixture was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether and the diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of a 50% sodium hydroxide solution. The basic solution (>pH 12) was extracted with ethyl acetate. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (3.56 g). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ammonium hydroxide; 85/14/1) to afford an oil (2.56 g) which was crystallized from diethyl ether to afford the title compound (2.40 g, 56%) mp=126-8°. Anal: C18H26N2O2Calc.: C 71.49; H 8.67; N 9.26; Found C 71.46; H 8.84; N 9.26. evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid The acidic solution was extracted with diethyl ether The acidic aqueous layer was basified by dropwise addition of a 50% sodium hydroxide solution The basic solution (>pH 12) was extracted with ethyl acetate The ethyl acetate layer was washed with distilled water dried (Na2SO4) filtered evaporated

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl]ethanal (2.50 g, 14.28 mmol) and 4-acetamidopiperidine AcOH (2.88 g, 14.28 mmol) (preparation described in U.S. Pat. No. 5,028,616) in ethanol (80 ml) under a nitrogen atmosphere, borane/pyridine complex (1.5 ml, 15 mmol) was added. The reaction mixture was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether and the diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of a 50% sodium hydroxide solution. The basic solution (>pH 12) was extracted with ethyl acetate. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (3.56 g). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ammonium hydroxide; 85/14/1) to afford an oil (2.56 g) which was crystallized from diethyl ether to afford the title compound (2.40 g, 56%) mp=126-8°. Anal: C18H26N2O2Calc.: C 71.49; H 8.67; N 9.26; Found C 71.46; H 8.84; N 9.26. evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid The acidic solution was extracted with diethyl ether The acidic aqueous layer was basified by dropwise addition of a 50% sodium hydroxide solution The basic solution (>pH 12) was extracted with ethyl acetate The ethyl acetate layer was washed with distilled water dried (Na2SO4) filtered evaporated

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanol (1.45 g, 8 mmol), N-methylmorpholine-N-oxide (1.41 g, 12 mmol) and 4 A molecular sieves (4.0 g) in methylene chloride (20 ml), tetrapropylammonium perruthenate (0.140 g, 0.4 mmol) was added. The reaction mixture was stirred at room temperature for 15 min., diluted with an equal volume of ethyl acetate (20 ml) and flash filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1). Concentration of the filtrate in vacuo afforded the title compound as an oily gum (0.92 g, 64%). NMR (300 MHz/CDCl3) 9.87 (1 H, s). filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1)

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanol (1.45 g, 8 mmol), N-methylmorpholine-N-oxide (1.41 g, 12 mmol) and 4 A molecular sieves (4.0 g) in methylene chloride (20 ml), tetrapropylammonium perruthenate (0.140 g, 0.4 mmol) was added. The reaction mixture was stirred at room temperature for 15 min., diluted with an equal volume of ethyl acetate (20 ml) and flash filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1). Concentration of the filtrate in vacuo afforded the title compound as an oily gum (0.92 g, 64%). NMR (300 MHz/CDCl3) 9.87 (1 H, s). filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1)

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanol (1.45 g, 8 mmol), N-methylmorpholine-N-oxide (1.41 g, 12 mmol) and 4 A molecular sieves (4.0 g) in methylene chloride (20 ml), tetrapropylammonium perruthenate (0.140 g, 0.4 mmol) was added. The reaction mixture was stirred at room temperature for 15 min., diluted with an equal volume of ethyl acetate (20 ml) and flash filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1). Concentration of the filtrate in vacuo afforded the title compound as an oily gum (0.92 g, 64%). NMR (300 MHz/CDCl3) 9.87 (1 H, s). filtered through silica gel (eluant: methylene chloride/ethyl acetate 1:1)

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

Procedure: To a stirred solution of 2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethanal (875 mg, 5 mmol) and 4-(2-benzofurancarboxamido)piperidine hydrochloride (1.4 g, 5 mmol)under a nitrogen atmosphere, borane/pyridine complex (0.5 ml, excess) was added. The reaction was stirred overnight (ca 15 h) and evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid. The acidic solution was extracted with diethyl ether. The diethyl ether extracts were discarded. The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide. The ethyl acetate layer was washed with distilled water, dried (Na2SO4), filtered and evaporated to afford an oily gum (520 mg). The resulting gum was purified by chromatography on silica (eluant: chloroform/ethanol/ammonium hydroxide; 85/14/1) to afford an oil (260 mg) which was crystallized from diethyl ether to afford the title compound (150 mg, 7%), mp=146°-8°. Anal: C25H28N2O3 0.5 H2O, Calc. C, 72.62; H, 7.07; N, 6.77; Found C,72.40; H, 6.94; N, 6.83. evaporated to an oily gum which was neutralized by careful addition of 10% hydrochloric acid The acidic solution was extracted with diethyl ether The acidic aqueous layer was basified by dropwise addition of 50% sodium hydroxide The ethyl acetate layer was washed with distilled water dried (Na2SO4) filtered evaporated