3,4-dihydro-2H-chromene-2-carbaldehyde

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl)tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate (1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl) tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)-methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate(1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl)tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate (1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl) tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)-methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate(1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl) tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)-methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate(1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl)tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate(1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl)tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate(1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3.4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl)tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: C2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1 ) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)-methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate(1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: C2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: To a stirred solution of 8 parts of (-)-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid in 225 parts of tetrahydrofuran were added 7.2 parts of 1,1'-carbonylbis[1H-imidazole]. After stirring for 1 hour at room temperature, the whole was cooled to -65° C. and 84 parts of a solution of bis(2-methylpropyl)aluminum hydride 1.5M in methylbenzene were added dropwise during a 10 minutes-period. Upon completion, stirring was continued for 15 minutes at -65° C. After the addition of 16 parts of methanol, the reaction mixture was poured onto water. The whole was acidified and the product was extracted with 1,1'-oxybisethane. The extract was washed with water, dried, filtered and evaporated. The residue was purified by filtration over silica gel using trichloromethane as eluent. The pure fractions were collected and the eluent was evaporated, yielding 6.6 parts (65%) of (-)-3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde as a residue; [α]D =-97.96° (c=1% in CH3OH) (intermediate 50). the whole was cooled to -65° C. Upon completion, stirring was continued for 15 minutes at -65° C the reaction mixture was poured onto water the product was extracted with 1,1'-oxybisethane The extract was washed with water dried filtered evaporated The residue was purified by filtration over silica gel The pure fractions were collected the eluent was evaporated

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

Procedure: To a stirred solution of 12 parts of (+)-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid in 270 parts of tetrahydrofuran were added 11 parts of 1,1'-carbonylbis[1H-imidazole]. After stirring for 1 hour at room temperature, the whole was cooled to -70° C. and 84 parts of a solution of bis(2-methylpropyl)aluminum hydride 1.5M in methylbenzene were added dropwise. Upon completion, stirring was continued for 20 minutes at -70° C. After the addition of 40 parts of methanol, the reaction mixture was poured onto water. The whole was acidified and the product was extracted with 1,1'-oxybisethane. The extract was washed with water, dried, filtered and evaporated. The residue was purified by filtration over silica gel using trichloromethane as eluent. The pure fractions were collected and the eluent was evaporated, yielding 9.50 parts (84% ) of (+)-3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde as a residue; [α]D =+94.8° (c=1% in CH3OH) (intermediate 49). the whole was cooled to -70° C. Upon completion, stirring was continued for 20 minutes at -70° C the reaction mixture was poured onto water the product was extracted with 1,1'-oxybisethane The extract was washed with water dried filtered evaporated The residue was purified by filtration over silica gel The pure fractions were collected the eluent was evaporated

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl)tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate (1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2 /(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)

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

Procedure: A mixture of 3,4-dihydro-2H-1-benzopyran-2-carboxaldehyde (0.015 mol) and 1-(3-aminopropyl) tetrahydro-2(1H)-pyrimidinethione (0.01 mol) in methanol (150 ml) was hydrogenated for 2 days at room temperature (atmospheric pressure) with palladium on activated carbon (2 g) as a catalyst. After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5). The pure fractions were collected and the solvent was evaporated. The residue (0.3 g) was dissolved in ethanol (30 ml) and converted into the ethanedioic acid salt (1:1) with ethanedioic acid (0.3 g; 0.0124 mol). The precipitate was filtered off and dried (vacuum), yielding 0.3 g (7%) of (±)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)-methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinethione ethanedioate(1:1); mp. 217.6° C. (comp. 14). After uptake of H2 (1 eq.), the catalyst was filtered off the filtrate was evaporated The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 95/5) The pure fractions were collected the solvent was evaporated The residue (0.3 g) was dissolved in ethanol (30 ml) The precipitate was filtered off dried (vacuum)