1,4-dihydroisochromen-3-one

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: A solution of 0.256 g of (E)-3-[2-[4-(cyclobutyl)-2-thiazolyl]ethenyl]benzeneamine and 0.148 g of 3-isochromanone was heated in a 126° C. oil bath for 17 hr. The residual materials were purified by silica gel chromatography using ethyl acetate-hexane (1:4 v/v) as the eluant to yield (E)-2-[2-[3-[2-[4-(cyclobutyl)-2-thiazolyl]ethenyl]phenylamino]-2-oxoethyl]benzyl alcohol. The residual materials were purified by silica gel chromatography

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

Procedure: Gaseous hydrogen chloride was bubbled through a solution of 3-isochromanone (2.0 g, 13.5 mmol) in methanol (30 ml) for 0.5 hour at room temperature and the reaction stirred for a further 2 hours. The methanol was removed under reduced pressure and the residue was dissolved in dichloromethane and dried. Removal of the solvent gave methyl 2-chloromethylphenylacetate (2.62 g, 98%) as an oil which was used without further purification; 1H NMR (270 MHz)δ: 3.70(3H,s), 3.81(2H,s), 4.68(2H,s), 7.22-7.40(4H,m) ppm. The methanol was removed under reduced pressure the residue was dissolved in dichloromethane dried Removal of the solvent

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

Procedure: Gaseous hydrogen chloride was bubbled through a solution of 3-isochromanone (2.0 g, 13.5 mmol) in methanol (30 ml) for 0.5 hour at room temperature and the reaction stirred for a further 2 hours. The methanol was removed under reduced pressure and the residue was dissolved in dichloromethane and dried. Removal of the solvent gave methyl 2-chloromethylphenylacetate (2.62 g, 98%) as an oil which was used without further purification; 1H NMR (270 MHz)δ: 3.70(3H,s), 3.81(2H,s), 4.68(2H,s), 7.22-7.40(4H,m) ppm. The methanol was removed under reduced pressure the residue was dissolved in dichloromethane dried Removal of the solvent

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

Procedure: After the completion of reaction, the concentration of 3-isochromanone was analyzed by GC analysis and then the yield of 3-isochromanone was calculated. As a result, the yield was found to be 75% based on α-chloro-α′-cyano-o-xylene. At this time, the conversion ratio of α-chloro-α′-cyano-o-xylene was 100% and the by-product α-hydroxy-α′-cyano-o-xylene was produced in a yield of 2.2%. Furthermore, as a result of the HPLC analysis, α-carboxy-α′-hydroxy-o-xylene and α-aminocarboxy-α′-hydroxy-o-xylene were found to be present as by-products in a concentration of 18% based on α-chloro-α′-cyano-o-xylene. After the completion of reaction

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

Procedure: After completion of the reaction, the concentration of 3-isochromanone was analyzed by GC analysis and then the yield of 3-isochromanone was calculated. As a result, the yield was found to be 95% based on α-chloro-α′-cyano-o-xylene. At this time, the conversion ratio of α-chloro-α′-cyano-o-xylene was 100% and the by-product compound (α-hydroxy-α′-cyano-o-xylene) where the halogen moiety was hydrolyzed was produced in a yield of 1.6%. After completion of the reaction

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

Procedure: After the reaction, recovery of isochromanones can be carried out by concentration of reaction mixture or extraction with an organic solvent such as ethyl acetate, toluene, xylene and ethylbenzene. When the reaction mixture is separated into two layers, i.e., a water layer and a product layer, depending on the target isochromanones, it is possible to separate and remove the water layer. In particular, when the product is 3-isochromanone, the product layer is liquid at 85° C. or higher, so that solubility in water is low and the target compound can be recovered by separation operation. Further, distillation and purification under reduced pressure can give rise to highly pure 3-isochromanone. When the reaction mixture is separated into two layers, i.e. to separate remove the water layer at 85° C. the target compound can be recovered by separation operation Further, distillation and purification under reduced pressure

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

Procedure: After the reaction, recovery of isochromanones can be carried out by concentration of reaction mixture or extraction with an organic solvent such as ethyl acetate, toluene, xylene, ethylbenzene, or methylene chloride. When the reaction mixture is separated into two layers, i.e., a water layer and a product layer, depending on the target isochromanones, it is possible to separate and remove the water layer. In particular, when the product is 3-isochromanone, the product layer is liquid at 85° C. or higher, so that solubility in water is low and the target compound can be recovered by separation operation. Further, distillation and purification under reduced pressure can give rise to highly pure 3-isochromanone. When the reaction mixture is separated into two layers, i.e. to separate remove the water layer at 85° C. the target compound can be recovered by separation operation Further, distillation and purification under reduced pressure

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

Procedure: Recovery of isochromanones after the reaction is possible by concentration of reaction mixture or extraction with organic solvents such as ethyl acetate, methylene chloride, toluene, xylene, and ethylbenzene. Depending on the target isochromanones, when there are two layers, i.e., water layer and product layer, it is possible to separate the water layer and remove it. In particular, when the product is 3-isochromanone, the product layer is liquid at 85° C. or higher, and the solubility in water is low so that the target compound can be recovered by the operation of separation. Further, it is possible to obtain high purity 3-isochromanone by distillation purification under reduced pressure. to separate the water layer remove it at 85° C. can be recovered by the operation of separation

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

Procedure: A solution of 0.256 g of (E)-3-[2-[4-(cyclobutyl)-2-thiazolyl]ethenyl]benzeneamine and 0.148 g of 3-isochromanone was heated in a 126° C. oil bath for 17 hr. The residual materials were purified by silica gel chromatography using ethyl acetate-hexane (1:4 v/v) as the eluant to yield (E)-2-[2-[3-[2-[4-(cyclobutyl)-2-thiazolyl]ethenyl]phenylamino]-2-oxoethyl]benzyl alcohol. The residual materials were purified by silica gel chromatography

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

Procedure: Hydrogen chloride gas was bubbled though a solution of 3-isochromanone (1.2 g, 8.1 mmol) in methanol (30 mL) for 3 minutes. Reaction stirred at room temperature for 8 hours. Mixture was diluted with water (70 mL). Mixture was extracted with dichloromethane (2×40 mL). Combined organic layers were washed with brine (20 mL). Mixture was dried (magnesium sulfate), filtered and concentrated in vacuo. Title compound was obtained as clear colorless oil in 90% yield. 1H NMR (300 MHz, CDCl3): δ=7.40-7.26 (m, 4H), 4.67 (s, 2H), 3.80 (s, 2H), 3.69 (s, 3H). Reaction Mixture was extracted with dichloromethane (2×40 mL) Combined organic layers were washed with brine (20 mL) Mixture was dried (magnesium sulfate) filtered concentrated in vacuo