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Chemical Structure| 3246-03-5

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Product Details of [ 3246-03-5 ]

CAS No. :3246-03-5
Formula : C16H19NO2
M.W : 257.33
SMILES Code : COC1=CC=CC=C1OCCNCC2=CC=CC=C2

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Application In Synthesis of [ 3246-03-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 3246-03-5 ]

[ 3246-03-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 3246-03-5 ]
  • [ 51997-51-4 ]
  • [ 72955-94-3 ]
YieldReaction ConditionsOperation in experiment
99% With potassium carbonate; In water; at 20 - 90℃; for 3h; Step 3: Preparation of N-Benzyl carvedilol; Epoxy carbazole (100g) obtained in step 2 was charged to water (500ml) under stirring followed by potassium carbonate (112g) and N-[2-(2-methoxy-phenoxy)ethyl]- benzylamine (140g) at room temperature. The contents were heated to 80 - 90C and stirred for 3 hours at 85 - 90C. The reaction mass was cooled to 30 - 35C and water was decanted. Fresh water (1L) was added and the mass stirred to obtain a solid which was filtered and washed with water to obtain the title compound (205g) (99%).
Example 1; To 400 ml ethylacetate, 70 g (0.27 moles) of anhydrous N-2- [2- (methoxy)-phenoxy]- ethyl]-benzylamine, 10.25 g (0.075 moles) of anhydrous ZnCl2 and 50 g (0.21 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70- 75C for 3 hrs (TLC control for checking conversion to N-benzylcarvedilol). The reaction mixture is cooled to ambient temperature and quenched into 100 ml OF-12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered. To this solution OF N-BENZYL CARVEDILOL IN ethylacetate, (7g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4. 5 K G/CM2 at temperature of 60-70C for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to remove ethylacetate. To the resultant syrupy mass n- butanol (100 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (50 ml) and toluene (50 ml) to obtain carvedilol (47 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (42 g). Example 10 To 400 ml ethylacetate, 70 g (0.27 moles) anhydrous N-2-[2-(METHOXY)-PHENOXY]-ETHYL]- benzylamine, 10.25 g (0.075 moles) of anhydrous ZnCl2 and 50 g (0.21 moles) OF 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70- 75C for 3 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture is cooled to ambient temperature and quenched into 100 ml OF-12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered and the filtrate subjected to hydrogenation reaction. To this solution of N-benzyl carvedilol in ethylacetate, (7 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 4.0 Kg/cm2 at temperature of 60-70C for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to about 3-4 volumes of the original volume and left for crystallisation of crude carvedilol for a period of about 10 hrs and filtered to obtain cravedilol (50 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (42 g).Example 11 To 400 ml ethylacetate, 70 g (0.27 moles) anhydrous N-2- [2- (metlioxy)-phenoxy]-ethyl]- benzylamine, 10.25 g (0.075 moles) of anhydrous ZnCl2 and 50 g (0.21 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70- 75C for 3 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture is cooled to ambient temperature and quenched into 100 ml OF-12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered and the filtrate subjected to hydrogenation reaction. To this solution of N-benzyl carvedilol in ethylacetate, 5 ml acetic acid is added, followed by (7 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 4.0 K G/CM2 at temperature of 60-70C for a period of about 8 hours. The reaction mixture is filtered and the filtrate is washed with 40 ml of 12-15% v/v aqueous ammonia. The product enriched organic layer is separated and concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (100 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (50 ml) and toluene (100 ml) to obtain carvedilol (55.4 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (49 g).
With trifluoroacetic acid; In 1,4-dioxane; at 70 - 75℃; for 48h; Example 7; To 8 ml ethylacetate 1.4 g (0.0054 moles) of anhydrous N-2- [2- (METHOXY)-PHENOXY]- ethyl]-benzylamine, 0.15 g (0.0013 moles) trifluoroacetic acid and 0.5 g (0.0021 moles) of 4-(OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70-75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To this reaction mixture, a second lot of 0.15 g (0.0013 moles) of trifluoroacetic acid and 0.5 G (0.0021 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to 70-75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture can be further subjected to hydrogenation reaction as described above in example 4.
With trifluoroacetic acid; In 1,4-dioxane; at 70 - 75℃; for 48h; Example 9; To 5 ml dioxane 1.4 g (0.0054 moles) of anhydrous N-2- [2- (METHOXY)-PHENOXY]-ETHYL]- benzylamine, 0.15 g (0.0013 moles) of trifluoroacetic acid and 0. 5 g (0.0021 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70- 75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To this reaction mixture, a second lot of 0.15 g (0.0013 moles) of trifluoroacetic acid and 0.5 g (0.0021 moles) OF 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to 70-75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture can be further subjected to hydrogenation reaction as described above in example 6, after distilling off dioxane and adding 10 ml ethylacetate.
With trifluoroacetic acid; In 1,2-dimethoxyethane; at 70 - 75℃; for 48h; Example 8; To 5 ml dimethoxyethane 1.4 g (0.0054 moles) of anhydrous N-2- [2- (METHOXY)- phenoxy]-ethyl]-benzylamine, 0.15 g (0.0013 moles) of trifluoroacetic acid and 0.5 g (0.0021 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70-75C for 24 hrs (TLC control for checking conversion to N- benzyl carvedilol). To this reaction mixture, a second lot of 0.15 g (0.0013 moles) of trifluoroacetic acid and 0.5 g (0.0021 moles) of 4-(OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to 70-75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture can be further subjected to hydrogenation reaction after distilling off dimethoxyethane and adding 10 ml ethylacetate, as described above in example 5.
With water; In 1,4-dioxane; at 78 - 80℃; for 31h; Example 13; To 400 ml dioxane, 80.6 g (0.31 moles) of N-2- [2- (METHOXY)-PHENOXY]-ETHYL]- benzylamine (moisture content 15%), 25 ml Water and 25 g (0.105 moles) of 4- (OXIRANYLMETLLOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 78- 80C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To this reaction mixture, a second lot of 25 ml Water and 25 g (0.105 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to 78-80C for 7 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture can be further subjected to hydrogenation reaction as described in example 6, after distilling off dioxane and adding ethylacetate.
With acetic acid; In ethyl acetate; for 48h;Heating / reflux; Example 4 To 450 ml ethylacetate, 70 g (0.27 moles) of anhydrous N-2- [2- (METHOXY)-PHENOXY]- ETHYL] -BENZYLAMINE, 3.65 G (0.06 MOLES) OF ACETIC ACID AND 25 G (0.105 MOLES) OF 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to reflux for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To the above reaction mixture, a second lot of 3.65 g (0.06 moles) of acetic acid and 25 g (0.105 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to reflux for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). The reaction mixture is cooled to ambient temperature and subjected to hydrogenation reaction. To this solution of N-benzyl carvedilol in ethylacetate, (7 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4. 5 KG/CM2 at temperature of 60-70C for a period of about 8 hours. The reaction mixture is filtered and the filtrate is washed with 12-15% V/V aqueous ammonia (1 volume w. R. t. to the carbazole). The product enriched organic layer is separated and concentrated to remove ethylacetate. To the resultant syrupy mass n- butanol (100 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (50 ml) and toluene (50 ml) to obtain carvedilol (45 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (41 g).Example 12; To 450 ml ethylacetate, 82.5 g (0.27 moles, on dry basis) of N-2- [2- (methoxy)-phenoxy]- ETHYL] -BENZYLAMINE (MOISTURE CONTENT 15%), 3. 65 G (0.06 MOLES) OF ACETIC ACID AND 25 G (0.105 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to reflux for 24 hrs (TLC control for checking conversion of to N-benzyl carvedilol). To the above reaction mixture, a second lot of 3.65 g (0.06 moles) of acetic acid and 25 g (0.105 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to reflux for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). The. reaction mixture is cooled to ambient temperature and subjected to hydrogenation reaction as described in example 4 above.
With acetic acid; In 1,4-dioxane; at 70 - 75℃; for 48h; Example 6; To 5 ml dioxane 1.4 g (0.0054 moles) of anhydrous N-2- [2- (methoxy)-phenoxy]-ethyl]- benzylamine, 0.07 g (0.00125 moles) of acetic acid and 0.5 g (0.0021 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70- 75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To this reaction mixture, a second lot of 0.07 g (0.00125 moles) of acetic acid and 0.5 g (0.0021 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to 70-75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). Dioxane is distilled off from the reaction mixture and to, the concentrated reaction mixture 10 ml ethylacetate is added and subjected the reaction mass to hydrogenation. To this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4. 5 Kg/cm2 at temperature of 60-70C for a period of about 8 hours. The reaction mixture is filtered and the filtrate is washed with 12-15% v/v aqueous ammonia (1 volume w. R. t. to the carbazole). The product enriched organic layer is separated and concentrated to remove ethylacetate. To the resultant syrupy mass n- butanol (2 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (1 ml) and toluene (1 ml) to obtain carvedilol (0.9 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (0.75 g).
With acetic acid; In 1,2-dimethoxyethane; at 70 - 75℃; for 48h; Example 5 To 5 ml dimethoxyethane, 1.4 g (0.0054 moles) of anhydrous N-2- [2- (METHOXY)- PHENOXY] -ETHYL] -BENZYLAMINE, 0.07 G (0.00125 MOLES) OF ACETIC ACID AND 0.5 G (0.0021 moles) 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE ARE added and the reaction mixture is heated to 70-75C for 24 hrs (TLC control for checking conversion to N-benzyl carvedilol). To this reaction mixture, a second lot of 0.07 g (0.00125 moles) of acetic acid and 0.5 g (0.0021 moles) OF 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is further heated to 0-75C for 24 hrs (TLC control for checking conversion of to N- benzyl carvedilol). Dimethoxyethane is distilled off from the reaction mixture and to the concentrated reaction mixture 10 ml ethylacetate is added and subjected the reaction mass to hydrogenation. To this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4. 5 KG/CM2 at temperature of 60-70C for A period of about 8 hours. The reaction mixture is filtered and the filtrate is washed with 12-15% v/v aqueous ammonia (1 volume w. R. t. to the carbazole). The product enriched organic layer is separated and concentrated to remove ethylacetate. To the resultant syrupy mass n- butanol (2 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (1 ml) and toluene (1 ml) to obtain carvedilol (0.9 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (0.75 g).
Example 3 To 5 ml Dioxane 1.4 g (0.0054 moles) of anhydrous N-2-[2-(METHOXY)-PHENOXY]-ETHYL]- benzylamine, 0.21 g (0.0015 moles) of anhydrous ZnCl2 and 1 g (0.0042 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70- 75C for 2.5 hrs (TLC control for checking conversion to N-benzyl carvedilol). The dioxane is distilled off from the reaction mixture and to the concentrated mass is added 10 ml ethylacetate, followed by 2 ml OF-12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered. To this solution of N-benzyl carvedilol in ethylacetate, (0.14 g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4. 5 KG/CM2 at temperature OF 60-70C for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (2 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (1 ml) and toluene (1 ml) to obtain carvedilol (0.9 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (0.8 g).
Example 2 To 250 ml dimethoxyethane, 70 g (0.27 moles) of anhydrous N-2- [2- (methoxy)- phenoxy]-ethyl]-benzylamine, 10.25 g (0.075 moles) of anhydrous ZnCl2 and 50 g (0.21 moles) of 4- (OXIRANYLMETHOXY)-9H-CARBAZOLE are added and the reaction mixture is heated to 70-75C for 2.5 hrs (TLC control for checking conversion to N-benzyl carvedilol). Dimethoxyethane is distilled off from the reaction mixture and to the concentrated mass is added 400 ml ethylacetate, followed by 100 ml OF-12-15% aqueous ammonia. The aqueous layer separated, and the product enriched organic layer is washed with water till neutral pH. The organic layer is charcoalised, filtered. To this solution of N-benzyl carvedilol in ethylacetate, (7g) of wet Pd/C catalyst (5% Pd content and 50% moisture content) is added. The reaction mixture is hydrogenated at 3.5-4. 5 KG/CM2 at temperature of 60-70C for a period of about 10 hours. The reaction mixture is filtered and filtrate concentrated to remove ethylacetate. To the resultant syrupy mass n-butanol (100 ml) is added and the solution is stirred for about 10 hours, the crystals separated by filtration, washed successively with n-butanol (50 ml) and toluene (50 ml) to obtain carvedilol (50 g). The product is recrystallized from 3 volumes of ethyl acetate to obtain carvedilol (45 g).
51.0 g (82%) In ethanol; Example 15 1-{Benzyl-[2-(2-methoxy-phenoxy)-ethyl]-amino}-3-(9H-carbazol-4-yloxy)-propan-2-ol 35.0 g of benzyl-[2-(2-methoxy-phenoxy)-ethyl]-amine (136 mmol) were dissolved in 225 ml ethanol. To the stirred solution 30.1 g of <strong>[51997-51-4]4-oxiranylmethoxy-9H-carbazole</strong> (126 mmol) were added and the mixture was heated under reflux for 15 h. The boiling solution was treated with 3 g of activated carbon for 30 min. The activated carbon was filtered off in the heat, and washed with 20 ml ethanol. The solution was stirred for 3 h at room temperature and next 5 h at 0 C. The product was filtered under suction and washed twice with 10 ml cold ethanol. The substance was dried at 50 C. for 12 h Yield: 51.0 g (82%), purity 99.3% according to HPLC analysis.

 

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