1-(1-benzofuran-2-yl)ethanone

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: Racemic 4-benzofuran-2-yl-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline was prepared from 2-acetylbenzofuran and 3-tolylmethylamine as described in Example 26. This racemic compound (105 mg) was separated on semi-prep chiral HPLC (chiralcel OD-H, 1×25 cm, eluent: 3% ethanol in heptane, flow: 4 ml/minute, 500 μl injections, 5 mg/injections). The resulting free bases were dissolved in ethyl acetate and treated with a 2 M solution of HCl in diethyl ether (2 equiv) to give (+)-4-benzofuran-2-yl-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline, hydrochloride salt (39 mg, 100% AUC HPLC, 99.4% AUC chiral HPLC): 1H NMR (300 MHz, Acetone-d6) δ7.63-7.70 (m, 1H), 7.20-7.47 (m, 6H), 7.00-7.08 (m, 2H), 5.31-5.43 (m, 1H), 4.43-4.62 (m, 2H), 3.70-3.88 (m, 2H), 3.01 (s, 3H); EI MS m/z=277 [C19H19NO]+, [α]25D+20° (c 1.0, MeOH, free base) and (−)-4-benzofuran-2-yl-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline, hydrochloride salt (40 mg, 100% AUC HPLC, 100% chiral HPLC): 1H NMR (300 MHz, Acetone-d6) δ7.63-7.69 (m, 1H), 7.21-7.47 (m, 6H), 7.00-7.10 (m, 2H), 5.32-5.45 (m, 1H), 4.43-4.66 (m, 2H), 3.67-3.90 (m, 2H), 3.02 (s, 3H); EI MS m/z=277 [C19H19NO]+; [α]25D−17° (c 1.0, MeOH, free base). This racemic compound (105 mg) was separated on semi-prep chiral HPLC (chiralcel OD-H, 1×25 cm, eluent: 3% ethanol in heptane, flow: 4 ml/minute, 500 μl injections, 5 mg/injections) The resulting free bases were dissolved in ethyl acetate

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

Procedure: Benzofuran-2-yl methyl ketone (1.60 g, 10 mM) was dissolved in ether (20 mL). Under stirring of the mixture at room temperature, bromine (1.60 g) was added thereto. The resultant mixture was stirred for 10 minutes at room temperature, and poured in saturated sodium hydrogencarbonate solution, followed by extraction with ether (80 mL). The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was removed. Hexane was added to the residue and crystals were collected through filtration. The crystals were washed with hexane and dried, whereby 1.55 g of the product of interest was obtained (yield 69.4%). followed by extraction with ether (80 mL) The extract was washed with saturated brine dried over magnesium sulfate the solvent was removed Hexane was added to the residue and crystals were collected through filtration The crystals were washed with hexane dried

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

Procedure: Benzofuran-2-yl methyl ketone (1.60 g, 10 mM) was dissolved in ether (20 mL). Under stirring of the mixture at room temperature, bromine (1.60 g) was added thereto. The resultant mixture was stirred for 10 minutes at room temperature, and poured in saturated sodium hydrogencarbonate solution, followed by extraction with ether (80 mL). The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was removed. Hexane was added to the residue and crystals were collected through filtration. The crystals were washed with hexane and dried, whereby 1.55 g of the product of interest was obtained (yield 69.4%). followed by extraction with ether (80 mL) The extract was washed with saturated brine dried over magnesium sulfate the solvent was removed Hexane was added to the residue and crystals were collected through filtration The crystals were washed with hexane dried

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

Procedure: n-Butyllithium (2.5M solution in hexane, 1 equivalent) was added dropwise to a solution of 4-methyl-2-trimethylsilylthiazole (1 equivalent) in dry diethyl ether at -70° C. under an atmosphere of dry nitrogen. After 30 minutes, 2-acetylbenzofuran (1 equivalent) in diethyl ether was added. After 1 hour the mixture was allowed to warm to room temperature and was then quenched by the addition of saturated aqueous sodium hydrogen carbonate. Work up in the normal fashion and column chromatography on silica gel then afforded the title compound. After 1 hour the mixture was allowed was then quenched by the addition of saturated aqueous sodium hydrogen carbonate

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

Procedure: Racemic 4-benzofuran-2-yl-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline was prepared from 2-acetylbenzofuran and 3-tolylmethylamine as described in Example 26. This racemic compound (105 mg) was separated on semi-prep chiral HPLC (chiralcel OD-H, 1×25 cm, eluent: 3% ethanol in heptane, flow: 4 ml/minute, 500 μl injections, 5 mg, injections). The resulting free bases were dissolved in ethyl acetate and treated with a 2 M solution of HCl in diethyl ether (2 equiv) to give (+)-4-benzofuran-2-yl-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline, hydrochloride salt (39 mg, 100% AUC HPLC, 99.4% AUC chiral HPLC): 1H NMR (300 MHz, Acetone-d6) δ7.63-7.70 (m, 1H), 7.20-7.47 (m, 6H), 7.00-7.08 (m, 2H), 5.31-5.43 (m, 1H), 4.43-4.62 (m, 2H), 3.70-3.88 (m, 2H), 3.01 (s, 3H); EI MS m/z=277 [C19H19NO]+, [α]25D +20° (c 1.0, MeOH, free base) and (−)-4-benzofuran-2-yl-2,7-dimethyl-1,2,3,4-tetrahydroisoquinoline, hydrochloride salt (40 mg, 100% AUC HPLC, 100% chiral HPLC): 1H NMR (300 MHz, Acetone-d6) δ7.63-7.69 (m, 1H), 7.21-7.47 (m, 6H), 7.00-7.10 (m, 2H), 5.32-5.45 (m, 1H), 4.43-4.66 (m, 2H), 3.67-3.90 (m, 2H), 3.02 (s, 3H); EI MS m/z=277 [C19H19NO]+; [α]25D −17° (c 1.0, MeOH, free base). This racemic compound (105 mg) was separated on semi-prep chiral HPLC (chiralcel OD-H, 1×25 cm, eluent: 3% ethanol in heptane, flow: 4 ml/minute, 500 μl injections, 5 mg, injections) The resulting free bases were dissolved in ethyl acetate

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

Procedure: Twenty six grams (g) (162 millimoles (mmol)) of commercially available 2-benzofuranylmethylketone was dissolved in 300 milliliters (ml) of methanol, and 16.9 g (243 mmol) of hydroxylamine hydrochloride and 20.4 g (243 mmol) of sodium hydrogencarbonate were added thereto. The resulting mixture was stirred at room temperature for 8 hours. Then, φml of water was added and the methanol was distilled away under reduced pressure. Precipitated crystals were filtered off and washed with water to yield 27.8 g of 2-benzofuranylmethylketone oxime having the following formula (yield, 98%). ##STR26## the methanol was distilled away under reduced pressure Precipitated crystals were filtered off washed with water

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

Procedure: Twenty six grams (g) (162 millimoles (mmol)) of commercially available 2-benzofuranylmethylketone was dissolved in 300 milliliters (ml) of methanol, and 16.9 g (243 mmol) of hydroxylamine hydrochloride and 20.4 g (243 mmol) of sodium hydrogencarbonate were added thereto. The resulting mixture was stirred at room temperature for 8 hours. Then, φml of water was added and the methanol was distilled away under reduced pressure. Precipitated crystals were filtered off and washed with water to yield 27.8 g of 2-benzofuranylmethylketone oxime having the following formula (yield, 98%). ##STR26## the methanol was distilled away under reduced pressure Precipitated crystals were filtered off washed with water

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylhydrazine (97%; 6.3 ml, 1 eq) is introduced into a solution of 2-acetylbenzofuran (10 g, 1 eq) in ethanol (25 ml). After adding 20 drops of glacial acetic acid, the mixture is stirred at 80° C. for 1 h. Subsequently, the solvent is distilled off. The residue is introduced gradually into polyphosphoric acid (100 g), heated to 120° C. and stirred for 1 h. The reaction output is added cautiously to ice-water and neutralized with 2M NaOH. The precipitate is filtered off and washed with distilled water. The residue is dried under reduced pressure. After recrystallization in ethyl acetate/n-hexane, 7.0 g are obtained. Yield: 48% Subsequently, the solvent is distilled off The residue is introduced gradually into polyphosphoric acid (100 g) heated to 120° C. stirred for 1 h The reaction output is added cautiously to ice-water and neutralized with 2M NaOH The precipitate is filtered off washed with distilled water The residue is dried under reduced pressure After recrystallization in ethyl acetate/n-hexane 7.0 g are obtained

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Phenylhydrazine (97%; 6.3 ml, 1 eq) is introduced into a solution of 2-acetylbenzofuran (10 g, 1 eq) in ethanol (25 ml). After adding 20 drops of glacial acetic acid, the mixture is stirred at 80° C. for 1 h. Subsequently, the solvent is distilled off. The residue is introduced gradually into polyphosphoric acid (100 g), heated to 120° C. and stirred for 1 h. The reaction output is added cautiously to ice-water and neutralized with 2M NaOH. The precipitate is filtered off and washed with distilled water. The residue is dried under reduced pressure. After recrystallization in ethyl acetate/n-hexane, 7.0 g are obtained. Yield: 48% Subsequently, the solvent is distilled off The residue is introduced gradually into polyphosphoric acid (100 g) heated to 120° C. stirred for 1 h The reaction output is added cautiously to ice-water and neutralized with 2M NaOH The precipitate is filtered off washed with distilled water The residue is dried under reduced pressure After recrystallization in ethyl acetate/n-hexane 7.0 g are obtained