2-amino-1-(2-fluorophenyl)ethanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-hydroxy-2-(2-fluorophenyl)ethanamine (1.54 g) and 4-methylphenylacetone (1.48 g) was refluxed in benzene (70 ml) under Dean & Stark conditions for 4h. The solvent was removed under reduced pressure, replaced with methanol and sodium borohydride (3 g) added portionwise. The solvent was evaporated under reduced pressure, the residue partitioned between water and ether and the ether layer dried (MgSO4). Removal of the solvent under reduced pressure gave an oil which was chromatographed on Kieselgel 60. Elution with 1% methanol-chloroform gave the title compound (1.58 g) as a 49:51 mixture of diastereoisomers, mp 65-68 (hexane). The solvent was removed under reduced pressure added portionwise The solvent was evaporated under reduced pressure the residue partitioned between water and ether the ether layer dried (MgSO4) Removal of the solvent under reduced pressure gave an oil which was chromatographed on Kieselgel 60 Elution with 1% methanol-chloroform

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-hydroxy-2-(2-fluorophenyl)ethanamine (1.54 g) and 4-methylphenylacetone (1.48 g) was refluxed in benzene (70 ml) under Dean & Stark conditions for 4h. The solvent was removed under reduced pressure, replaced with methanol and sodium borohydride (3 g) added portionwise. The solvent was evaporated under reduced pressure, the residue partitioned between water and ether and the ether layer dried (MgSO4). Removal of the solvent under reduced pressure gave an oil which was chromatographed on Kieselgel 60. Elution with 1% methanol-chloroform gave the title compound (1.58 g) as a 49:51 mixture of diastereoisomers, mp 65-68 (hexane). The solvent was removed under reduced pressure added portionwise The solvent was evaporated under reduced pressure the residue partitioned between water and ether the ether layer dried (MgSO4) Removal of the solvent under reduced pressure gave an oil which was chromatographed on Kieselgel 60 Elution with 1% methanol-chloroform

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This was prepared in an identical manner to the compound described in Example 1 using 2-hydroxy-2-(2-fluorophenyl) ethanamine (1.55 g) and 4-{(E)-2-carbomethoxyethenyl}phenylpropan-2-one (2.18 g). Elution with 1% methanolchloroform on Kieselgel 60 gave the title compound (1.2 g) m.p. 111°-116° C. (benzene-heptane) as an ~40:60 mixture of diastereoisomers. τ(CDCl3) 8.95 (3H, d, J=6 Hz), 6.85-7.7 (7H, m, 2H disappears with D2O), 6.25 (3H, s), 5.1 (1H, m), 3.6 (1H, d, J=16 Hz), 2.5-3.2 (8H, m), 2.35 (1H, d, J=16 Hz). This was prepared in an identical manner to the compound Elution with 1% methanolchloroform on Kieselgel 60

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: This was prepared in an identical manner to the compound described in Example 1 using 2-hydroxy-2-(2-fluorophenyl) ethanamine (1.55 g) and 4-{(E)-2-carbomethoxyethenyl}phenylpropan-2-one (2.18 g). Elution with 1% methanolchloroform on Kieselgel 60 gave the title compound (1.2 g) m.p. 111°-116° C. (benzene-heptane) as an ~40:60 mixture of diastereoisomers. τ(CDCl3) 8.95 (3H, d, J=6 Hz), 6.85-7.7 (7H, m, 2H disappears with D2O), 6.25 (3H, s), 5.1 (1H, m), 3.6 (1H, d, J=16 Hz), 2.5-3.2 (8H, m), 2.35 (1H, d, J=16 Hz). This was prepared in an identical manner to the compound Elution with 1% methanolchloroform on Kieselgel 60

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-(4-carbomethoxymethoxyphenyl)propan-2-one (2.22 g) and 2-hydroxy-2-(2-fluorophenyl)ethanamine (1.55 g) in benzene (100 ml) was boiled under reflux with azeotropic removal of water using a Dean and Stark trap, for 2 hours. The solution was cooled, evaporated to dryness, the residue dissolved in methanol and sodium borohydride (500 mg) added. After 30 minutes, the methanol was evaporated and the residue partitioned between ethyl acetate and water. The organic layer was dried (magnesium sulphate) and evaporated to leave an oil which was chromatographed on silica gel 60 eluting with 2% methanol/chloroform. N-[2-(4-(2-hydroxyethoxy)phenyl-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine (300 mg) crystallised from hexane, m.p. 80°-95°, as a 55:45 mixture of diastereoisomers. The solution was cooled evaporated to dryness the residue dissolved in methanol sodium borohydride (500 mg) added After 30 minutes the methanol was evaporated the residue partitioned between ethyl acetate and water The organic layer was dried (magnesium sulphate) evaporated to leave an oil which was chromatographed on silica gel 60 eluting with 2% methanol/chloroform N-[2-(4-(2-hydroxyethoxy)phenyl-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine (300 mg) crystallised from hexane, m.p. 80°-95°, as a 55:45 mixture of diastereoisomers

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-(4-carbomethoxymethoxyphenyl)propan-2-one (2.22 g) and 2-hydroxy-2-(2-fluorophenyl)ethanamine (1.55 g) in benzene (100 ml) was boiled under reflux with azeotropic removal of water using a Dean and Stark trap, for 2 hours. The solution was cooled, evaporated to dryness, the residue dissolved in methanol and sodium borohydride (500 mg) added. After 30 minutes, the methanol was evaporated and the residue partitioned between ethyl acetate and water. The organic layer was dried (magnesium sulphate) and evaporated to leave an oil which was chromatographed on silica gel 60 eluting with 2% methanol/chloroform. N-[2-(4-(2-hydroxyethoxy)phenyl-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine (300 mg) crystallised from hexane, m.p. 80°-95°, as a 55:45 mixture of diastereoisomers. The solution was cooled evaporated to dryness the residue dissolved in methanol sodium borohydride (500 mg) added After 30 minutes the methanol was evaporated the residue partitioned between ethyl acetate and water The organic layer was dried (magnesium sulphate) evaporated to leave an oil which was chromatographed on silica gel 60 eluting with 2% methanol/chloroform N-[2-(4-(2-hydroxyethoxy)phenyl-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine (300 mg) crystallised from hexane, m.p. 80°-95°, as a 55:45 mixture of diastereoisomers

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Trimethylsilyl cyanide (8.5 g) was added to a stirred mixture of 2-fluorobenzaldehyde (10.6 g) and zinc iodide (500 mg) in dry ether (150 ml). The mixture was stirred at ambient temperature for 24 hours and was then added dropwise to a stirred suspension of lithium aluminium hydride (3.2 g) in dry ether (50 ml) under nitrogen. The mixture was refluxed for 2 hours, cooled and water (3.2 ml), 2 N sodium hydroxide solution (3.2 ml) and water (9.6 ml) slowly added. The precipitate was filtered off, the filtrate was dried (MgSO4) and evaporated to a yellow oil (13.0 g) which crystallised slowly on standing. The mixture was refluxed for 2 hours cooled The precipitate was filtered off the filtrate was dried (MgSO4) evaporated to a yellow oil (13.0 g) which crystallised slowly