1-phenylhexan-2-one

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:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 240 mg of sodium hydride as a suspension at 50% in oil were added to a solution of 0.81 g of 1-phenyl-2-hexanone of Step A of Example 7 in 20 ml of tetrahydrofuran and the mixture was stirred for 90 minutes at 40° C. Then, a solution of 900 mg of 4-(bromomethyl)-benzonitrile in 10 ml of tetrahydrofuran was added and after stirring for 2 hours at ambient temperature, the reaction mixture was poured into water. Extraction was carried out with ethyl acetate and the extracts were washed with water, dried, and evaporated to dryness. The residue was chromatographed on silica (eluant: methylene chloride--hexane (1-1)) to obtain 1.1 g of the desired product melting at 70° C. after stirring for 2 hours at ambient temperature Extraction the extracts were washed with water dried evaporated to dryness The residue was chromatographed on silica (eluant: methylene chloride--hexane (1-1))

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

実験手順: 100 ml of n-tetrabutyl tin, then 120 mg of [benzyl (chloro) bis(triphenyl phosphine)]palladium were added to a solution of 40 ml of phenyl acetyl chloride in 500 ml of tetrahydrofuran. The mixture was stirred for 15 hours at reflux, filtered on clarcel and evaporated to dryness. The residue was distilled at 65° C. to 68° C. under 0.5 mm of mercury and the main fraction was chromatographed on silica (eluant: hexane--ethyl acetate (9-1)) to obtain 27.5 g of the desired product. at reflux filtered on clarcel evaporated to dryness The residue was distilled at 65° C. to 68° C. under 0.5 mm of mercury the main fraction was chromatographed on silica (eluant: hexane--ethyl acetate (9-1))

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

実験手順: To an ice-cold magnetically stirred mixture of 1-phenylhexan-2-one (Intermediate II-1) (7.04 gram, 0.04 mol) and sodium methoxide (4.32 g, 0.08 mol) was added dropwise 2-iodopropane (15 ml) in a nitrogen atmosphere. The resulting mixture was heated for 1 hour at reflux temperature. The obtained mixture was allowed to attain room temperature and concentrated. The resulting residue was taken up in diethyl ether and water. The diethyl ether layer was separated and successively washed with an aqueous Na2S2O3 solution and water. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was further purified using Sepacore equipment: (petroleum ether/diethyl ether=19/1 (v/v)) to give 2-methyl-3-phenyl-octan-4-one (Intermediate IIa-1) (3.52 gram) as a colorless oil; 1H-NMR (400 MHz, CDCl3) δ 0.66 (d, J=7, 3H), 0.81 (t, J=7, 3H), 0.96 (d, J=7, 3H), 1.10-1.24 (m, 2H), 1.36-1.54 (m, 2H), 2.29-2.47 (m, 3H), 3.30 (d, J=10 Hz, 1H), 7.20-7.33 (m, 5H). Rf (petroleum ether/diethyl ether=98/2 (v/v))˜0.25. The resulting mixture was heated for 1 hour at reflux temperature to attain room temperature concentrated The diethyl ether layer was separated successively washed with an aqueous Na2S2O3 solution and water The organic layer was dried over Na2SO4 filtered concentrated The residue was further purified

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

実験手順: Part B: To a magnetically stirred solution of pentanoic acid methoxy-methyl-amide (8.6 g, 59.3 mmol) at 0° C. in anhydrous THF (100 ml) was slowly added benzylmagnesium chloride (2 M solution in THF, 45 ml, 90 mmol) and the resulting mixture was reacted for 20 hours in a nitrogen atmosphere at room temperature. The reaction mixture was poured in excess of a cold (0° C.) aqueous hydrochloric acid (4 N solution) and extracted with MTBE. The organic layer was dried over Na2SO4, filtered and concentrated to give crude product. This crude product was further purified using Sepacore equipment: Gradient: (petroleum ether/diethyl ether=98/2 (v/v))=>(petroleum ether/diethyl ether=95/5 (v/v)) to give 1-phenylhexan-2-one (Intermediate II-1) (7.38 gram, 71% yield) as a colorless oil; 1H-NMR (400 MHz, CDCl3) δ 0.86 (t, J=7, 3H), 1.21-1.31 (m, 2H), 1.48-1.58 (m, 2H), 2.41-2.47 (m, 2H), 3.68 (s, 2H), 7.18-7.36 (m, 5H). at 0° C. the resulting mixture was reacted for 20 hours in a nitrogen atmosphere at room temperature extracted with MTBE The organic layer was dried over Na2SO4 filtered concentrated to give crude product This crude product was further purified

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 240 mg of sodium hydride as a suspension at 50% in oil were added to a solution of 0.81 g of 1-phenyl-2-hexanone of Step A of Example 7 in 20 ml of tetrahydrofuran and the mixture was stirred for 90 minutes at 40° C. Then, a solution of 900 mg of 4-(bromo-methyl)-benzonitrile in 10 ml of tetrahydrofuran was added and after stirring for 2 hours at ambient temperature, the reaction mixture was poured into water. Extraction was carried out with ethyl acetate and the extracts were washed with water, dried, and evaporated to dryness. The residue was chromatographed on silica (eluant: methylene chloride - hexane (1-1)) to obtain 1.1 g of the desired product melting at 70° C. after stirring for 2 hours at ambient temperature Extraction the extracts were washed with water dried evaporated to dryness The residue was chromatographed on silica (eluant: methylene chloride - hexane (1-1))

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

実験手順: 100 ml of n-tetrabutyl tin, then 120 mg of [benzyl (chloro) bis(triphenyl phosphine)]palladium were added to a solution of 40 ml of phenyl acetyl chloride in 500 ml of tetrahydrofuran. The mixture was stirred for 15 hours at reflux, filtered on clarcel and evaporated to dryness. The residue was distilled at 65° C. to 68° C. under 0.5 mm of mercury and the main fraction was chromatographed on silica (eluant: hexane - ethyl acetate (9-1)) to obtain 27.5 g of the desired product. at reflux filtered on clarcel evaporated to dryness The residue was distilled at 65° C. to 68° C. under 0.5 mm of mercury the main fraction was chromatographed on silica (eluant: hexane - ethyl acetate (9-1))