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CAS No. : | 36669-02-0 | MDL No. : | MFCD22490931 |
Formula : | C10H10O5 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | BQGDDMMXPRJQHZ-UHFFFAOYSA-N |
M.W : | 210.18 | Pubchem ID : | 12223651 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.9 g | With sodium hydrogencarbonate In N,N-dimethyl-formamide at 55℃; for 3 h; | A mixture of 3-hydroxyphtalic anhydride (1.6 g, 9.8 mmol) in MeOH (25 mL) was refluxed for 3 hours. The mixture was cooled to room temperature and concentrated. The residue and NaHC03 (2.3 g, 27.3 mmol) were stirred in DMF (20 mL). Methyl iodide (1.46 mL, 23.4 mmol) was added and the reaction mixture was heated at 55 °C for 3 hours. The reaction was cooled to room temperature and diluted with EtOAc (80 mL) and water (40 mL). The mixture was acidified with an aqueous solution of HCI (4N) and the aqueous layer was extracted with EtOAc (2 x 40 mL). The combined organic layers were washed with water (2 x 100 mL), brine (2 x 100 mL) and dried over MgS04. The solvent was removed in vacuo and the crude product was purified by flash column . chromatography with 3:7 EtOAc: Petrol to give 1 ,2-dimethyl 3-hydroxybenzene-1 ,2-dicarboxylate (1.9 g, 9.1 mmol, 94percent) as a pale pink oil. H NMR (400 MHz, DMSO-cf6) δ ppm 10.28 (s, 1 H), 7.44-7.30 (m, 2H), 7.17 (dd, J = 7.1 , 2.2 Hz, 1 H), 3.80 (s, 3H), 3.77 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ ppm 167.61 , 166.10, 155.04, 130.96, 129.04, 122.99, 120.92, 120.42, 52.90, 52.53. LC-MS: [M+H]+ = 211 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sodium hydrogencarbonate In N,N-dimethyl-formamide at 50 - 55℃; for 2 - 4 h; | Example 3 4-Benzyloxy-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[169] A mixture of 3-hydroxyphthalic anhydride (4.96 g, 30.2 mmol) in methanol(60 mL) was refluxed for 3 h, cooled to room temperature, and the solvent was evaporated under vacuum. The residue and sodium bicarbonate (7.11 g, 84.6 mmol) were suspended in DMF (40 mL). Iodomethane (4.53 mL, 72.5 mmol) was added and the reaction mixture was heated at 50 0C for 2 h. The solvent was removed under vacuum and the residue was partitioned between ethyl acetate (120 mL) and water (100 mL). The organic phase was washed with water (2 x 100 mL) and evaporated. The residue was chromatographed using a hexanes-ethyl acetate gradient, eluting the product at 6:4 hexanes-ethyl acetate, 4.83 g of 3- hydroxy-phthalic acid dimethyl ester, in 76percent yield; 1H NMR (CDCl3) δ 3.89 (s, 3H), 3.92 (s, 3H), 6.97 (dd, J = 7.9 Hz, J = 0.9 Hz, IH), 7.09 (dd, J = 8.6 Hz, J = 1.0 Hz, IH), 7.46 (t, J = 8.3 Hz, IH), 10.58 (s, IH). Example 242-(2,6-Dioxo-piperidin-3-yl)-4-(4-methoxy-benzyloxy)-isoindole-l,3-dioneStep 1 :[232] A stirred mixture of 3-hydroxyphthalic anhydride (20.5 g, 125 mmol) in methanol (100 mL) was heated to reflux for three hours. The solvent was evaporated in vacuo, and the residue was suspended in sodium bicarbonate (29.4 g, 350 mmol) in DMF (250 mL), followed by addition of iodomethane (19 mL, 300 mmol) and heating at 550C for four hours. The mixture was cooled to room temperature, solvent evaporated in vacuo, and <n="78"/>the residue was partitioned between water (200 mL) and ethyl acetate (200 mL). The organic layer was washed with water (2 x 200 mL), dried, concentrated in vauco, and then purified by flash column chromatography (Silica Gel, EtOAc/Hexane, 0percent gradient to 100percent 30 min) to give 3-hydroxyphthalic acid dimethyl ester (20.2 g, 77percent yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; | Step 2:[170] Potassium carbonate (1.78 g, 12.9 mmol) and benzyl bromide (0.92 mL, 7.7 mmol) were added to a stirred solution of 3-hydroxy-phthalic acid dimethyl ester (1.35 g, 6.40 mmol) in DMF (15 mL). The reaction mixture was stirred overnight at room temperature and then quenched with cold water (60 mL). The aqueous layer was extracted with ethyl acetate (3 x 40 mL). The combined organic layers were washed with water (4 x 50 mL) and brine (50 mL), dried (MgSO4) and the solvent was evaporated under vacuum. The residue was chromatographed using a hexanes-ethyl acetate gradient, eluting the product at 7:3 hexanes-ethyl acetate, 1.66 g of 3-benzyloxy-phthalic acid dimethyl ester, in 86% yield; 1H NMR (CDCl3) delta 3.89 (s, 3H), 3.95 (s, 3H), 5.16 (s, 2H), 7.15 (d, J = 8.4 Hz, IH), 7.28-7.41 (m, 6H), 7.62 (d, J = 7.9 Hz, IH). |
With potassium carbonate; In N-methyl-acetamide; water; | Dimethyl 3-benzyloxyphthalate STR15 A mixture of 14.5 g (69 mmol) of <strong>[36669-02-0]dimethyl 3-hydroxyphthalate</strong>, 9.6 g (69 mmol) of anhydrous potassium carbonate and 8.23 ml (69 mmol) of benzyl bromide in 50 ml of dry dimethylformamide was heated with stirring at 80 C. After 18 hours the mixture was cooled and poured into 500 ml of water, and extracted into diethyl ether (3*100 ml). The combined organic extracts were dried and evaporated to yield the crude compound as an oil. Chromatography over silica gel eluding with hexane/diethyl ether (0->50%) gave the title compound as an oil. 1H-nmr delta (CDCl3): |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
toluene-4-sulfonic acid; In methanol; | Example 7-6 3-Hydroxyphthalic anhydride (1.0 g, 6.6 mmol) was dissolved in methanol (20 ml), and a catalytic amount of p-toluene sulfonic acid was added to this solution. The mixture was stirred with refluxing under heating for 5 hours, and concentrated under reduced pressure to give a crude product of dimethyl 3-hydroxyphthalate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; | The crude product of <strong>[36669-02-0]dimethyl 3-hydroxyphthalate</strong> was dissolved in DMF (20 ml), and potassium carbonate (6 g, 43 mmol) and n-amyl bromide (3 ml, 24 mmol) were added to this solution. The mixture was stirred at 90 C. for 1.5 hours, and solids were removed by filtration through Celite. The filtrate was concentrated under reduced pressure to give a crude product of dimethyl 3-pentyloxyphthalate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In butanone; | The starting material can be prepared as follows: 225 g of potassium carbonate and 98 g of allyl bromide are added to a solution of 170.0 g of <strong>[36669-02-0]dimethyl 3-hydroxy-phthalate</strong> in 400 ml of methyl ethyl ketone. The mixture is heated to the reflux temperature for 18 hours, whilst stirring, and then filtered, the filter residue is washed with methyl ethyl ketone and the filtrate, combined with the wash liquid, is evaporated under reduced pressure. The residual oily crude product is distilled under reduced pressure; dimethyl 3-allyloxyphthalate is obtained as the main fraction; boiling point 126-130/0.015 mm Hg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone;Heating / reflux; | Example 9 4-(3-Bromo-benzyloxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[187] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.3 g, 6.2 mmol) in acetone (30 mL) and potassium carbonate (2.5 g, 18.4 mmol) was added 3- bromobenzyl bromide (1.6 g, 6.4 mmol) and refiuxed overnight. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL) and washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(3- bromo-benzyloxy)-phthalic acid dimethyl ester (2.5 g, 109% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone; for 3h;Heating / reflux; | Example 12 2-(2,6-Dioxo-piperidin-3-yl)-4-(3-methoxy-benzyloxy)-isoindole-l,3-dioneStep 1:[196] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.1 g, 5.2 mmol) in acetone (45 mL) and potassium carbonate (2.2 g, 15.7 mmol) was added 1- bromomethyl-3-methoxy-benzene (0.77 mL, 5.5 mmol) and refluxed for three hours. The solvent was evaporated and the residue was partitioned between water (50 mL) and ethyl acetate (80 mL) and washed with water (2 x 50 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(3-methoxy-benzyloxy)-phthalic acid dimethyl ester (2.1 g, 118% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone; for 6h;Heating / reflux; | Step 2:[233] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.1 g, 5.2 mmol) in acetone (45 mL) and potassium carbonate (2.2 g, 15.7 mmol), was added 1- bromomethyl-4-methoxy-benzene (0.79 mL, 5.5 mmol). The mixture was refluxed for six hours. The solvent was evaporated in vacuo, and the residue was partitioned between water (50 mL) and ethyl acetate (80 mL). The organic layer was washed with water (2 x 50 mL), dried, concentrated in vacuo, and purified by flash column chromatography (Silica Gel, EtOAc/Hexane, 0% gradient to 100% 30 min) to give 3-(4-methoxy-benzyloxy)-phthalic acid dimethyl ester (2.0 g, 115% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 50 - 55℃; for 2 - 4h;Product distribution / selectivity; | Example 3 4-Benzyloxy-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[169] A mixture of 3-hydroxyphthalic anhydride (4.96 g, 30.2 mmol) in methanol(60 mL) was refluxed for 3 h, cooled to room temperature, and the solvent was evaporated under vacuum. The residue and sodium bicarbonate (7.11 g, 84.6 mmol) were suspended in DMF (40 mL). Iodomethane (4.53 mL, 72.5 mmol) was added and the reaction mixture was heated at 50 0C for 2 h. The solvent was removed under vacuum and the residue was partitioned between ethyl acetate (120 mL) and water (100 mL). The organic phase was washed with water (2 x 100 mL) and evaporated. The residue was chromatographed using a hexanes-ethyl acetate gradient, eluting the product at 6:4 hexanes-ethyl acetate, 4.83 g of 3- hydroxy-phthalic acid dimethyl ester, in 76% yield; 1H NMR (CDCl3) delta 3.89 (s, 3H), 3.92 (s, 3H), 6.97 (dd, J = 7.9 Hz, J = 0.9 Hz, IH), 7.09 (dd, J = 8.6 Hz, J = 1.0 Hz, IH), 7.46 (t, J = 8.3 Hz, IH), 10.58 (s, IH). Example 242-(2,6-Dioxo-piperidin-3-yl)-4-(4-methoxy-benzyloxy)-isoindole-l,3-dioneStep 1 :[232] A stirred mixture of 3-hydroxyphthalic anhydride (20.5 g, 125 mmol) in methanol (100 mL) was heated to reflux for three hours. The solvent was evaporated in vacuo, and the residue was suspended in sodium bicarbonate (29.4 g, 350 mmol) in DMF (250 mL), followed by addition of iodomethane (19 mL, 300 mmol) and heating at 550C for four hours. The mixture was cooled to room temperature, solvent evaporated in vacuo, and <n="78"/>the residue was partitioned between water (200 mL) and ethyl acetate (200 mL). The organic layer was washed with water (2 x 200 mL), dried, concentrated in vauco, and then purified by flash column chromatography (Silica Gel, EtOAc/Hexane, 0% gradient to 100% 30 min) to give 3-hydroxyphthalic acid dimethyl ester (20.2 g, 77% yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone;Heating / reflux; | Example 10 2-(2,6-Dioxo-piperidin-3-yl)-4-(3-methyl-benzyIoxy)-isoindole-l,3-dioneStep 1 :[190] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.4 g, 6.4 mmol) in acetone (30 mL) and potassium carbonate (2.7 g, 19.3 mmol) was added 1- bromomethyl-3 -methyl-benzene (0.91 mL, 6.7 mmol) and refluxed overnight. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL) and washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(3- methyl-benzyloxy)-phthalic acid dimethyl ester (2.3 g, 115% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone;Heating / reflux; | Example 8 4-(3-Fluoro-benzyloxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[184] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.4 g, 6.7 mmol) in acetone (30 mL) and potassium carbonate (2.8 g, 20 mmol) was added 3- fluorobenzyl bromide (0.89 mL, 7.0 mmol) and refluxed overnight. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL) and washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(3- fluoro-benzyloxy)-phthalic acid dimethyl ester (2.4 g, 113% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium carbonate; In acetone;Heating / reflux; | Example 4 4-(3-Chloro-benzyloxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindoIe-l,3-dioneStep 1 :[173] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.3 g, 6.3 mmol) in acetone (20 mL) and potassium carbonate (2.1 g, 15.2 mmol) was added 3- chlorobenzyl bromide (1.0 mL, 7.6 mmol) and refluxed overnight. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL), and washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(3- chloro-benzyloxy)-phthalic acid dimethyl ester (1.9 g, 92% yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone; for 2h;Heating / reflux; | Example 22 4-(5-Chloro-thiophen-2-ylmethoxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[226] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.4 g, 6.8 mmol) in acetone (70 mL) and potassium carbonate (2.8 g, 20 mmol) was added 2-chloro-5- chloromethyl-thiophene (0.83 mL, 7.1 mmol) and refluxed for two hours. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL) and washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(5- chloro-thiophen-2-ylmethoxy)-phthalic acid dimethyl ester (2.3 g, 100% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 17h; | Step 2:[212] A mixture of polymer-supported PPh3 (3.1 g, ~ 9.5 mmol) and benzofuran-2- yl-methanol (0.70 g, 4.8 mmol) in 20 mL THF was cooled to 0 0C under N2. Diisopropylazodicarboxylate (1.9 g, 9.5 mmol) was added dropwise, and subsequently 3- <n="70"/>hydroxy-phthalic acid dimethyl ester (1.0 g, 4.8 mmol) was added as a solid. The mixture stirred for an additional hour at 0 0C and was then allowed to warm to room temperature. After stirring for 16 h, the mixture was filtered. The filter was washed with ethyl acetate (25 mL) and the combined filtrates were evaporated. The residue was dissolved in 75 mL ethyl acetate and washed with Na2CO3 (2 x 75 mL) and water (2 x 75 mL), dried (MgSO4), and evaporated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone;Heating / reflux; | Example 11 2-(2,6-Dioxo-piperidin-3-yl)-4-(4-methanesulfonyl-benzyloxy)-isoindole-l,3-dioneStep 1 :[193] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.3 g, 6.1 mmol) in acetone (25 mL) and potassium carbonate (2.5 g, 18 mmol) was added 1- bromomethyl-4-rnethanesulfbnyl-benzene (1.6 g, 6.4 mmol) and refluxed overnight. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL) and washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(4-methanesulfonyl-benzyloxy)-phthalic acid dimethyl ester (2.4 g, 104% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; | Example 13 4-(Benzo [ 1 ,3] dioxol-5-y lmethoxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l ,3-dioneStep 1 :[199] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.0 g, 4.8 mmol), benzo[l,3]dioxol-5-yl-methanol (1.4 g, 9.5 mmol), and polymer-supported triphenyl phosphine (3.0 g, 9.5 mmol) in THF (30 mL) in an ice-bath was slowly added diisopropyl azodicarboxylate (1.9 mL, 9.5 mmol) and stirred at r.t. overnight. The mixture was filtered and the filter was washed with ethyl acetate (10 mL). The filtrate was evaporated and the residue was purified by flash column chromatography (EtOAc/Hexane) to give 3- (benzo[l,3]dioxol-5-ylmethoxy)-phthalic acid dimethyl ester (1.7 g, 102% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 17h; | Example 23 2-(2,6-Dioxo-piperidin-3-yl)-4-(l-naphthalen-2-yl-ethoxy)-isoindole-l,3-dioneStep 1 :[229] A mixture of polymer-supported PPh3 (3.1 g, ~ 9.5 mmol) and alpha-methyl-2- naphthalenemethanol (0.82 g, 4.8 mmol) in 20 mL THF was cooled to 0 0C under N2. Diisopropylazodicarboxylate (1.9 g, 9.5 mmol) was added dropwise, and subsequently 3- hydroxy-phthalic acid dimethyl ester (1.0 g, 4.8 mmol) was added as a solid. The mixture stirred for an additional hour at 0 0C and was then allowed to warm to room temperature. After stirring for 16 h, the mixture was filtered. The filter was washed with ethyl acetate (20 mL) and the combined filtrates were evaporated. The residue was chromatographed in hexanes-ethyl acetate gradient, eluting 1.2 g of the 3-(l-naphthalen-2-yl-ethoxy)-phthalic acid dimethyl ester at 20-30% ethyl acetate, in 66% yield; 1H NMR (DMSO-d6) delta 1.70 (d, J = 6.5 Hz, 3H), 3.88 (s, 3H), 4.03 (s, 3H), 5.49 (q, J = 6.5 Hz, IH), 6.96 (d, J = 8.4 Hz, IH), 7.18 (t, J - 8.0 Hz, IH), 7.42-7.53 (m, 4H), 7.76-7.84 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 17h; | Step 2:[204] A mixture of polymer-supported PPh3 (3.1 g, ~ 9.5 mmol) and quinolin-3-yl- methanol (0.76 g, 4.8 mmol) in 20 mL THF was cooled to 0 0C under N2. Diisopropyl azodicarboxylate (1.9 g, 9.5 mmol) was added dropwise, and subsequently 3-hydroxy- phthalic acid dimethyl ester (1.0 g, 4.8 mmol) was added as a solid. The mixture stirred for an additional hour at 0 0C and was then allowed to warm to room temperature. After stirring for 16 h, the mixture was filtered. The filter was washed with ethyl acetate (25 mL) and the combined filtrates were evaporated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; | Example 7 4-(3,5-Dichloro-benzyloxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[181] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (0.5 g, 2.4 mmol), <strong>[60211-57-6](3,5-dichloro-phenyl)-methanol</strong> (0.84 g, 4.8 mmol), and polymer-supported triphenyl phosphine (1.5 g, 4.8 mmol) in THF (30 mL) in ice-bath was slowly added diisopropyl azodicarboxylate (1.0 mL, 4.8 mmol) and stirred at r.t. overnight. The mixture was filtered and the solid was washed with ethyl acetate (10 mL). The filtrate was evaporated and the residue was purified by flash column chromatography (EtOAc/Hexane) to give 3-(3,5-dichloro-benzyloxy)-phthalic acid dimethyl ester (0.42 g, 48% yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 17h; | Step 2:[208] A mixture of polymer-supported PPh3 (3.1 g, ~ 9.5 mmol) and quinolin-2-yl- methanol (0.76 g, 4.8 mmol) in 20 mL THF was cooled to 0 0C under N2. Diisopropylazodicarboxylate (1.9 g, 9.5 mmol) was added dropwise, and subsequently 3- hydroxy-phthalic acid dimethyl ester (1.0 g, 4.8 mmol) was added as a solid. The mixture stirred for an additional hour at 0 0C and was then allowed to warm to room temperature. After stirring for 16 h, the mixture was filtered. The filter was washed with ethyl acetate (25 mL) and the combined filtrates were evaporated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; | Step 2:[220] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.0 g, 4.8 mmol), (3-chloro-benzo[b]thiophen-2-yl)-methanol (1.9 g, 9.5 mmol), and polymer- supported triphenyl phosphine (3.0 g, 9.5 mmol) in THF (30 mL) in an ice-bath was slowly added diisopropyl azodicarboxylate (1.9 mL, 9.5 mmol) and stirred at r.t. overnight. The mixture was filtered and the solid was washed with ethyl acetate (10 mL). The filtrate was evaporated and the residue was purified by flash column chromatography (EtOAc/Hexane) to give 3-(3-chloro-benzo[b]thiophen-2-ylmethoxy)-phthalic acid dimethyl ester (2.1 g, 109% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 17h; | Example 18 4-(Benzo[b]thiophen-2-ylmethoxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[215] A mixture of polymer-supported PPh3 (3.1 g, ~ 9.5 mmol) and 1- benzothiophen-2-yl-methanol (1.0 g, 6.1 mmol) in 20 mL THF was cooled to 0 0C under N2. Diisopropylazodicarboxylate (1.9 g, 9.5 mmol) was added dropwise, and subsequently 3- hydroxy-phthalic acid dimethyl ester (1.0 g, 4.8 mmol) was added as a solid. The mixture stirred for an additional hour at 0 0C and was then allowed to warm to room temperature. After stirring for 16 h, the (mixture was filtered. The filter was washed with ethyl acetate (25 mL) and the combined filtrates were evaporated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium carbonate; In acetone;Heating / reflux; | Example 5 4-(4-Chloro-benzyloxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-l,3-dioneStep 1 :[176] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.3 g, 6.3 mmol) in acetone (20 mL) and potassium carbonate (2.6 g, 19 mmol) was added 4- chlorobenzyl chloride (1.1 g, 6.6 mmol) and refluxed overnight. The solvent was evaporated and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL) and <n="56"/>washed with water (2 x 100 mL). The combined organic phases was dried, concentrated and purified by flash column chromatography (EtOAc/Hexane) to give 3-(4-chloro-benzyloxy)- phthalic acid dimethyl ester (2.3 g, 110% crude yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With triphenylphosphine on polystyrene; di-isopropyl azodicarboxylate; In tetrahydrofuran; at 0 - 20℃; | Example 212-(2,6-Dioxo-piperidin-3-yI)-4-(4-fluoro-benzo[b]thiophen-2-ylmethoxy)- isoindole-l,3-dioneStep 1 :[223] To a stirred suspension of 3-hydroxyphthalic acid dimethyl ester (1.1 g, 5.2 mmol), (4-fluoro-benzo[b]thiophen-2-yl)-methanol (0.96 g, 10.5 mmol), and polymer- supported triphenyl phosphine (3.0 g, 10.5 mmol) in THF (35 mL) in an ice-bath was slowly added diisopropyl azodicarboxylate (2.1 mL, 10.5 mmol) and stirred at r.t. overnight. The mixture was filtered and the solid was washed with ethyl acetate (10 mL). The filtrate was evaporated and the residue was purified by flash column chromatography (EtOAc/Hexane) to give 3-(4-fluoro-benzo[b]thiophen-2-ylmethoxy)-phthalic acid dimethyl ester (1.5 g, 76% yield). The product was used in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | In methanol at 20 - 50℃; for 5h; Reflux; | 54.1 Step 1: Synthesis of 1,2-dimethyl 3-hydroxyphthalate. A solution of 4-hydroxy- 2-benzofuran-1,3-dione (1.0 g, 6.09 mmol) in methanol (12 mL) was heated atrefluxfor 3 h before cooling to RT. The solvent was removed under vacuum and solid sodium bicarbonate (1.43 g, 17.1 mmol) and DMF (8 mL) were added in this order. Next, iodomethane (0.91 mL, 14.6 mmol) was added and the reaction stirred at 50 °C for 2 hr. The solvent was removed, and the residue was partitioned between ethyl acetate (20 mL) and water (15 mL). The organics were washed twice more with water, dried over sodium sulfate, and filtered before purification using Chromatography A to afford the title compound (950 mg, 74%). |
74% | In methanol at 20 - 50℃; for 5h; Reflux; | 54.1 Step 1: Synthesis of 1,2-dimethyl 3-hydroxyphthalate. A solution of 4-hydroxy- 2-benzofuran-1,3-dione (1.0 g, 6.09 mmol) in methanol (12 mL) was heated atrefluxfor 3 h before cooling to RT. The solvent was removed under vacuum and solid sodium bicarbonate (1.43 g, 17.1 mmol) and DMF (8 mL) were added in this order. Next, iodomethane (0.91 mL, 14.6 mmol) was added and the reaction stirred at 50 °C for 2 hr. The solvent was removed, and the residue was partitioned between ethyl acetate (20 mL) and water (15 mL). The organics were washed twice more with water, dried over sodium sulfate, and filtered before purification using Chromatography A to afford the title compound (950 mg, 74%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.394 g | With caesium carbonate; In acetonitrile; at 80℃; for 32h; | tert-butyl (2-(2-chloroacetamido)ethyl)carbamate (0.66 g, 1 eq) was dissolved in MeCN (17 mL, 0.15 M). Dimethyl 3-hydroxyphthalate (0.578 g, 2.75 mmol, 1.1 eq) and cesium carbonate (2.24 g, 6.88 mmol, 2.75 eq) were then added. The flask was fitted with a reflux condenser and heated to 80 C for 32 hours. The mixture was then cooled to room temperature, diluted with EtOAc and washed three times with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (ISCO, 4g silica column, 0-15% MeOH/DCM over a 15 minute gradient) gave a yellow solid (0.394 g, 0.960 mmol, 38% over 2 steps). NMR (400 MHz, Chloroform- delta 7.65 - 7.56 (m, 1H), 7.50 - 7.41 (m, 1H), 7.27 (s, 1H), 7.11 (dd, J= 8.4, 4.1 Hz, 2H), 5.17 (s, 1H), 4.57 (d, J = 6.3 Hz, 2H), 3.94 (s, 2H), 3.88 (s, 2H), 3.40 (p, J= 5.8 Hz, 4H), 3.32 - 3.19 (m, 4H), 1.39 (d, J= 5.7 Hz, 13H). 13C NMR (100 MHz, cdch) delta 168.37, 168.23, 165.73, 156.13, 154.71, 131.24, 130.09, 124.85, 123.49, 117.24, 79.42, 68.48, 53.22, 52.83, 40.43, 39.54, 28.44. LCMS 411.45 (M+H). |
0.394 g | With caesium carbonate; In acetonitrile; at 80℃; for 32h; | tert-butyl (2-(2-chloroacetamido)ethyl)carbamate (0.66 g, 1 eq) was dissolved in MeCN (17 mL, 0.15 M). Dimethyl 3-hydroxyphthalate (0.578 g, 2.75 mmol, 1.1 eq) and cesium carbonate (2.24 g, 6.88 mmol, 2.75 eq) were then added. The flask was fitted with a reflux condenser and heated to 80 C. for 32 hours. The mixture was then cooled to room temperature, diluted with EtOAc and washed three times with water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (ISCO, 4 g silica column, 0-15% MeOH/DCM over a 15 minute gradient) gave a yellow solid (0.394 g, 0.960 mmol, 38% over 2 steps). 1H NMR (400 MHz, Chloroform-d) delta 7.65-7.56 (m, 1H), 7.50-7.41 (m, 1H), 7.27 (s, 1H), 7.11 (dd, J=8.4, 4.1 Hz, 2H), 5.17 (s, 1H), 4.57 (d, J=6.3 Hz, 2H), 3.94 (s, 2H), 3.88 (s, 2H), 3.40 (p, J=5.8 Hz, 4H), 3.32-3.19 (m, 4H), 1.39 (d, J=5.7 Hz, 13H). 13C NMR (100 MHz, cdcl3) delta 168.37, 168.23, 165.73, 156.13, 154.71, 131.24, 130.09, 124.85, 123.49, 117.24, 79.42, 68.48, 53.22, 52.83, 40.43, 39.54, 28.44. LCMS 411.45 (M+H). |
0.394 g | With caesium carbonate; In acetonitrile; at 80℃; for 32h; | tert-butyl (2-(2-chloroacetamido)ethyl)carbamate (0.66 g, 1 eq) was dissolved in MeCN (17 mL, 0.15 M). Dimethyl 3-hydroxyphthalate (0.578 g, 2.75 mmol, 1.1 eq) and cesium carbonate (2.24 g, 6.88 mmol, 2.75 eq) were then added. The flask was fitted with a reflux condenser and heated to 80 C for 32 hours. The mixture was then cooled to room temperature, diluted withEtOAc and washed three times with water. The organic layer was dried over sodium sulfate,filtered and concentrated under reduced pressure. Purification by column chromatography (ISCO,4g silica column, 0-15% MeOHIDCM over a 15 minute gradient) gave a yellow solid (0.394 g,0.960 mmol, 38% over 2 steps). 1H NMR (400 IVIFIz, Chloroform-cl) 7.65 - 7.56 (m, 1H), 7.50-7.41 (m, 1H), 7.27 (s, 1H), 7.11 (dd,J= 8.4, 4.1 Hz, 2H), 5.17 (s, 1H), 4.57 (d,J= 6.3 Hz, 2H),3.94 (s, 2H), 3.88 (s, 2H), 3.40 (p, J 5.8 Hz, 4H), 3.32-3.19 (m, 4H), 1.39 (d, J= 5.7 Hz, 13H).13CNMR(100 IVIHz, cdcl3) 168.37, 168.23, 165.73, 156.13, 154.71, 131.24, 130.09, 124.85, 123.49, 117.24, 79.42, 68.48, 53.22, 52.83, 40.43, 39.54, 28.44. LCMS 411.45 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With caesium carbonate; In acetonitrile; at 80℃; for 19h; | (2) Synthesis of dimethyl 3-((2,2-dimethyl-4,20-dioxo-3,9,12,15-tetraoxa-5,19-diazahenicosan- 21-yl)oxy)phthalate tert-butyl (1-chloro-2-oxo-7,10,13-trioxa-3-azahexadecan-16-yl)carbamate (1.41 g, 3.12 mmol, 1 eq) was dissolved in MeCN (32 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.721 g, 3.43 mmol, 1.1 eq) and cesium carbonate (2.80 g, 8.58 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 19 hours. The mixture was cooled to room temperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 24 g silica column, 0-15% MeOH/DCM 22 minute gradient) to give a yellow oil (1.5892 g, 2.78 mmol, 89% over two steps). 1H NMR (400 MHz, Chloroform-d) delta 7.52 (d, J = 7.8 Hz, 1H), 7.35 (t, J = 8.1Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H), 7.00 (t, J = 5.3 Hz, 1H), 5.06 (s, 1H), 4.46 (s, 2H), 3.83 (s, 3H), 3.78 (s, 3H), 3.47 (ddd, J = 14.9, 5.5, 2.8 Hz, 8H), 3.39 (dt, J = 9.4, 6.0 Hz, 4H), 3.29 (q, J = 6.5 Hz, 2H), 3.09 (d, J = 6.0 Hz, 2H), 1.70 (p, J = 6.5 Hz, 2H), 1.63 (p, J = 6.3 Hz, 2H), 1.31 (s, 9H).13C NMR (100 MHz, cdcl3) delta 167.68, 167.36, 165.45, 155.93, 154.41, 130.87, 129.60, 125.01, 123.20, 117.06, 78.60, 70.40, 70.17, 70.06, 69.39, 68.67, 68.25, 52.77, 52.57, 38.38, 36.58, 29.55, 29.20, 28.34. LCMS 571.47 (M+H). |
1.5892 g | With caesium carbonate; In acetonitrile; at 80℃; for 19h; | tert-butyl (l-chloro-2-oxo-7,10,13-trioxa-3-azahexadecan-16-yl)carbamate (1.41 g, 3.12 mmol, 1 eq) was dissolved in MeCN (32 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.721 g, 3.43 mmol, 1.1 eq) and cesium carbonate (2.80 g, 8.58 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 19 hours. The mixture was cooled to room temperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 24 g silica column, 0-15% MeOH/DCM 22 minute gradient) to give a yellow oil (1.5892 g, 2.78 mmol, 89% over two steps). NMR (400 MHz, Chloroform-i ) delta 7.52 (d, J = 7.8 Hz, 1H), 7.35 (t, J = 8.1 Hz, 1H), 7.04 (d, J= 8.3 Hz, 1H), 7.00 (t, J= 5.3 Hz, 1H), 5.06 (s, 1H), 4.46 (s, 2H), 3.83 (s, 3H), 3.78 (s, 3H), 3.47 (ddd, J = 14.9, 5.5, 2.8 Hz, 8H), 3.39 (dt, J = 9.4, 6.0 Hz, 4H), 3.29 (q, J= 6.5 Hz, 2H), 3.09 (d, J= 6.0 Hz, 2H), 1.70 (p, J = 6.5 Hz, 2H), 1.63 (p, J = 6.3 Hz, 2H), 1.31 (s, 9H). 13C NMR (100 MHz, cdcl3) delta 167.68, 167.36, 165.45, 155.93, 154.41, 130.87, 129.60, 125.01, 123.20, 117.06, 78.60, 70.40, 70.17, 70.06, 69.39, 68.67, 68.25, 52.77, 52.57, 38.38, 36.58, 29.55, 29.20, 28.34. LCMS 571.47 (M+H). |
1.5892 g | With caesium carbonate; In acetonitrile; at 80℃; for 19h; | tert-butyl (1-chloro-2-oxo-7,10,13-trioxa-3-azahexadecan-16-yl)carbamate (1.41 g, 3.12 mmol, 1 eq) was dissolved in MeCN (32 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.721 g, 3.43 mmol, 1.1 eq) and cesium carbonate (2.80 g, 8.58 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C. for 19 hours. The mixture was cooled to room temperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 24 g silica column, 0-15% MeOH/DCM 22 minute gradient) to give a yellow oil (1.5892 g, 2.78 mmol, 89% over two steps). (0684) 1H NMR (400 MHz, Chloroform-d) delta 7.52 (d, J=7.8 Hz, 1H), 7.35 (t, J=8.1 Hz, 1H), 7.04 (d, J=8.3 Hz, 1H), 7.00 (t, J=5.3 Hz, 1H), 5.06 (s, 1H), 4.46 (s, 2H), 3.83 (s, 3H), 3.78 (s, 3H), 3.47 (ddd, J=14.9, 5.5, 2.8 Hz, 8H), 3.39 (dt, J=9.4, 6.0 Hz, 4H), 3.29 (q, J=6.5 Hz, 2H), 3.09 (d, J=6.0 Hz, 2H), 1.70 (p, J=6.5 Hz, 2H), 1.63 (p, J=6.3 Hz, 2H), 1.31 (s, 9H). 13C NMR (100 MHz, cdcl3) delta 167.68, 167.36, 165.45, 155.93, 154.41, 130.87, 129.60, 125.01, 123.20, 117.06, 78.60, 70.40, 70.17, 70.06, 69.39, 68.67, 68.25, 52.77, 52.57, 38.38, 36.58, 29.55, 29.20, 28.34. LCMS 571.47 (M+H). |
1.5892 g | With caesium carbonate; In acetonitrile; at 80℃; for 19h; | tert-butyl (1 -chloro-2-oxo-7, 10,13 -trioxa-3 -azahexadecan- 1 6-yl)carbamate (1 .41 g, 3.12 mmol, 1 eq) was dissolved in MeCN (32 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.72 1 g, 3.43 mmol, 1.1 eq) and cesium carbonate (2.80 g, 8.58 mmol, 2.75 eq)were added. The flask was fitted with a reflux condenser and heated to 80 C for 19 hours. The mixture was cooled to roomtemperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 24 g silica column, 0-15% MeOHIDCM 22 minute gradient) to give a yellow oil (1.5892 g, 2.78 mmol, 89% over two steps).?HNMR (400 IVIHz, Chloroform-cl) 7.52 (d, J= 7.8 Hz, 1H), 7.35 (t, J 8.1 Hz, 1H), 7.04 (d, J= 8.3 Hz, 1H), 7.00 (t, J= 5.3 Hz, 1H), 5.06 (s, 1H), 4.46 (s, 2H), 3.83 (s, 3H), 3.78 (s, 3H), 3.47(ddd, J 14.9, 5.5, 2.8 Hz, 8H), 3.39 (dt, J 9.4, 6.0 Hz, 4H), 3.29 (q, J= 6.5 Hz, 2H), 3.09 (d, J= 6.0 Hz, 2H), 1.70 (p, J = 6.5 Hz, 2H), 1.63 (p, J = 6.3 Hz, 2H), 1.31 (s, 9H). 13CNMR(100IVIHz, cdcl3) 167.68, 167.36, 165.45, 155.93, 154.41, 130.87, 129.60, 125.01, 123.20, 117.06,78.60, 70.40, 70.17, 70.06, 69.39, 68.67, 68.25, 52.77, 52.57, 38.38, 36.58, 29.55, 29.20, 28.34.LCMS 571.47 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With caesium carbonate; In acetonitrile; at 80℃; for 14h; | tert-butyl (6-(2-chloroacetamido)hexyl)carbamate (0.2691 g, 0.919 mmol, 1 eq) was dissolved in MeCN (9.2 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.212 g, 1.01 mmol, 1.1 eq) and cesium carbonate (0.823 g, 2.53 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 14 hours. The mixture was cooled to room temperature and diluted with EtOAc, washed three times with water and back extracted once with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 12 g silica column, 0-15% MeOH/DCM 15 minute gradient) to give a yellow oil (0.304 g, 0.651 mmol, 71%). NMR (400 MHz, Chloroform-i ) delta 7.66 - 7.58 (m, 1H), 7.44 (td, J = 8.2, 1.6 Hz, 1H), 7.15 - 7.08 (m, 1H), 6.96 (s, 1H), 4.56 (s, 2H), 3.92 (t, J = 1.6 Hz, 3H), 3.88 (t, J= 1.6 Hz, 3H), 3.27 (q, J = 6.9 Hz, 2H), 3.10 - 3.00 (m, 2H), 1.41 (s, 13H), 1.33 - 1.22 (m, 4H). 13C NMR (100 MHz, cdch) delta 167.97, 167.37, 165.58, 155.95, 154.37, 130.97, 129.74, 124.94, 123.26, 116.81, 78.96, 68.04, 52.89, 52.87, 52.69, 52.67, 40.41, 38.96, 29.88, 29.13, 28.39, 26.33, 26.30. LCMS 467.49 |
71% | With caesium carbonate; In acetonitrile; at 80℃; for 14h; | tert-butyl (6-(2-chloroacetamido)hexyl)carbamate (0.2691 g, 0.919 mmol, 1 eq) was dissolved in MeCN (9.2 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.212 g, 1.01 mmol, 1.1 eq) and cesium carbonate (0.823 g, 2.53 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C. for 14 hours. The mixture was cooled to room temperature and diluted with EtOAc, washed three times with water and back extracted once with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 12 g silica column, 0-15% MeOH/DCM 15 minute gradient) to give a yellow oil (0.304 g, 0.651 mmol, 71%). 1H NMR (400 MHz, Chloroform-d) delta 7.66-7.58 (m, 1H), 7.44 (td, J=8.2, 1.6 Hz, 1H), 7.15-7.08 (m, 1H), 6.96 (s, 1H), 4.56 (s, 2H), 3.92 (t, J=1.6 Hz, 3H), 3.88 (t, J=1.6 Hz, 3H), 3.27 (q, J=6.9 Hz, 2H), 3.10-3.00 (m, 2H), 1.41 (s, 13H), 1.33-1.22 (m, 4H). 13C NMR (100 MHz, cdcl3) delta 167.97, 167.37, 165.58, 155.95, 154.37, 130.97, 129.74, 124.94, 123.26, 116.81, 78.96, 68.04, 52.89, 52.87, 52.69, 52.67, 40.41, 38.96, 29.88, 29.13, 28.39, 26.33, 26.30. LCMS 467.49. |
71% | With caesium carbonate; In acetonitrile; at 80℃; for 14h; | tert-butyl (6-(2-chloroacetamido)hexyl)carbamate (0.2691 g, 0.919 mmol, 1 eq) wasdissolved in MeCN (9.2 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.212 g, 1.01 mmol, 1.1 eq)and cesium carbonate (0.823 g, 2.53 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 14 hours. The mixture was cooled to room temperature and diluted with EtOAc, washed three times with water and back extracted once with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reducedpressure. The crude material was purified by column chromatography (ISCO, 12 g silica column,0-15% MeOH/DCM 15 minute gradient) to give a yellow oil (0.304 g, 0.65 1 mmol, 71%). ?HNMR (400 MHz, Chloroform-cl) 7.66-7.58 (m, 1H), 7.44 (td, J= 8.2, 1.6 Hz, 1H), 7.15-7.08(m, 1H), 6.96 (s, 1H), 4.56 (s, 2H), 3.92 (t, J= 1.6 Hz, 3H), 3.88 (t, J 1.6 Hz, 3H), 3.27 (q, J6.9 Hz, 2H), 3.10-3.00 (m, 2H), 1.41 (s, 13H), 1.33 - 1.22 (m, 4H). 13CNMR (100 MHz, cdcl3)167.97, 167.37, 165.58, 155.95, 154.37, 130.97, 129.74, 124.94, 123.26, 116.81, 78.96, 68.04,52.89, 52.87, 52.69, 52.67, 40.41, 38.96, 29.88, 29.13, 28.39, 26.33, 26.30. LCMS 467.49. |
71% | With caesium carbonate; In acetonitrile; at 80℃; for 14h; | (2) Synthesis of dimethyl 3-(2-((6-((tert-butoxycarbonyl)amino)hexyl)amino)-2- oxoethoxy)phthalate tert-butyl (6-(2-chloroacetamido)hexyl)carbamate (0.2691 g, 0.919 mmol, 1 eq) was dissolved in MeCN (9.2 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.212 g, 1.01 mmol, 1.1 eq) and cesium carbonate (0.823 g, 2.53 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 14 hours. The mixture was cooled to room temperature and diluted with EtOAc, washed three times with water and back extracted once with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 12 g silica column, 0-15% MeOH/DCM 15 minute gradient) to give a yellow oil (0.304 g, 0.651 mmol, 71%). 1H NMR (400 MHz, Chloroform-d) delta 7.66- 7.58 (m, 1H), 7.44 (td, J = 8.2, 1.6 Hz, 1H), 7.15- 7.08 (m, 1H), 6.96 (s, 1H), 4.56 (s, 2H), 3.92 (t, J = 1.6 Hz, 3H), 3.88 (t, J = 1.6 Hz, 3H), 3.27 (q, J = 6.9 Hz, 2H), 3.10- 3.00 (m, 2H), 1.41 (s, 13H), 1.33- 1.22 (m, 4H).13C NMR (100 MHz, cdcl3) delta 167.97, 167.37, 165.58, 155.95, 154.37, 130.97, 129.74, 124.94, 123.26, 116.81, 78.96, 68.04, 52.89, 52.87, 52.69, 52.67, 40.41, 38.96, 29.88, 29.13, 28.39, 26.33, 26.30. LCMS 467.49. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With caesium carbonate; In acetonitrile; at 80℃; for 18h; | tert-butyl (8-(2-chloroacetamido)octyl)carbamate (0.468 g, 1.46 mmol, 1 eq) was dissolved in MeCN (15 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.337 g, 1.60 mmol, 1.1 eq) and cesium carbonate (1.308 g, 4.02 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 18 hours. The mixture was cooled to room temperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 24 g silica column, 0-15% MeOH/DCM 20 minute gradient) to give a yellow oil (0.434 g, 0.878 mmol, 60%). NMR (400 MHz, Chloroform-i ) delta 7.57 (dd, J= 7.9, 0.8 Hz, 1H), 7.40 (t, J = 8.1 Hz, 1H), 7.07 (dd, J = 8.4, 0.7 Hz, 1H), 6.89 (t, J = 5.3 Hz, 1H), 4.63 (s, 1H), 4.52 (s, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.22 (q, J = 6.9 Hz, 2H), 3.01 (q, J = 6.4 Hz, 2H), 1.36 (s, 12H), 1.20 (s, 9H). 13C NMR (100 MHz, cdch) delta 167.89, 167.29, 165.54, 155.97, 154.38, 130.95, 129.69, 124.96, 123.23, 116.86, 78.82, 68.05, 52.83, 52.82, 52.66, 52.64, 40.54, 39.06, 29.97, 29.19, 29.10, 29.06, 28.40, 26.66, 26.61. LCMS 495.42 (M+H). |
60% | With caesium carbonate; In acetonitrile; at 80℃; for 18h; | tert-butyl (8-(2-chloroacetamido)octyl)carbamate (0.468 g, 1.46 mmol, 1 eq) was dissolved in MeCN (15 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.337 g, 1.60 mmol, 1.1 eq) and cesium carbonate (1.308 g, 4.02 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C. for 18 hours. The mixture was cooled to room temperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. (0726) The crude material was purified by column chromatography (ISCO, 24 g silica column, 0-15% MeOH/DCM 20 minute gradient) to give a yellow oil (0.434 g, 0.878 mmol, 60%). 1H NMR (400 MHz, Chloroform-d) delta 7.57 (dd, J=7.9, 0.8 Hz, 1H), 7.40 (t, J=8.1 Hz, 1H), 7.07 (dd, J=8.4, 0.7 Hz, 1H), 6.89 (t, J=5.3 Hz, 1H), 4.63 (s, 1H), 4.52 (s, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.22 (q, J=6.9 Hz, 2H), 3.01 (q, J=6.4 Hz, 2H), 1.36 (s, 12H), 1.20 (s, 9H). 13C NMR (100 MHz, cdcl3) delta 167.89, 167.29, 165.54, 155.97, 154.38, 130.95, 129.69, 124.96, 123.23, 116.86, 78.82, 68.05, 52.83, 52.82, 52.66, 52.64, 40.54, 39.06, 29.97, 29.19, 29.10, 29.06, 28.40, 26.66, 26.61. LCMS 495.42 (M+H). |
60% | With caesium carbonate; In acetonitrile; at 80℃; for 18h; | tert-butyl (8-(2-chloroacetamido)octyl)carbamate (0.468 g, 1.46 mmol, 1 eq) wasdissolved in MeCN (15 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.337 g, 1.60 mmol, 1.1 eq)and cesium carbonate (1.308 g, 4.02 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 18 hours. The mixture was cooled to room temperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure.The crude material was purified by column chromatography (ISCO, 24 g silica column, 0-15% MeOHIDCM 20 minute gradient) to give a yellow oil (0.434 g, 0.878 mmol, 60%). ?HNMR(400 IVIHz, Chloroform-cl) 7.57 (dd, J 7.9, 0.8 Hz, 1H), 7.40 (t, J 8.1 Hz, 1H), 7.07 (dd, J8.4, 0.7 Hz, 1H), 6.89 (t, J= 5.3 Hz, 1H), 4.63 (s, 1H), 4.52 (s, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.22(q, J= 6.9 Hz, 2H), 3.01 (q, J= 6.4 Hz, 2H), 1.36 (s, 12H), 1.20 (s, 9H). 13CNMR (100 IVIFIz,cdcl3) 167.89, 167.29, 165.54, 155.97, 154.38, 130.95, 129.69, 124.96, 123.23, 116.86, 78.82,68.05, 52.83, 52.82, 52.66, 52.64, 40.54, 39.06, 29.97, 29.19, 29.10, 29.06, 28.40, 26.66, 26.61.LCMS 495.42 (M+H). |
60% | With caesium carbonate; In acetonitrile; at 80℃; for 18h; | (2) Synthesis of dimethyl 3-(2-((8-((tert-butoxycarbonyl)amino)octyl)amino)-2- oxoethoxy)phthalate tert-butyl (8-(2-chloroacetamido)octyl)carbamate (0.468 g, 1.46 mmol, 1 eq) was dissolved in MeCN (15 mL, 0.1 M). Dimethyl 3-hydroxyphthalate (0.337 g, 1.60 mmol, 1.1 eq) and cesium carbonate (1.308 g, 4.02 mmol, 2.75 eq) were added. The flask was fitted with a reflux condenser and heated to 80 C for 18 hours. The mixture was cooled to room temperature and diluted water and extracted once with chloroform and twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (ISCO, 24 g silica column, 0- 15% MeOH/DCM 20 minute gradient) to give a yellow oil (0.434 g, 0.878 mmol, 60%). 1H NMR (400 MHz, Chloroform-d) delta 7.57 (dd, J = 7.9, 0.8 Hz, 1H), 7.40 (t, J = 8.1Hz, 1H), 7.07 (dd, J = 8.4, 0.7 Hz, 1H), 6.89 (t, J = 5.3 Hz, 1H), 4.63 (s, 1H), 4.52 (s, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.22 (q, J = 6.9 Hz, 2H), 3.01 (q, J = 6.4 Hz, 2H), 1.36 (s, 12H), 1.20 (s, 9H). 13C NMR (100 MHz, cdcl3) delta 167.89, 167.29, 165.54, 155.97, 154.38, 130.95, 129.69, 124.96, 123.23, 116.86, 78.82, 68.05, 52.83, 52.82, 52.66, 52.64, 40.54, 39.06, 29.97, 29.19, 29.10, 29.06, 28.40, 26.66, 26.61. LCMS 495.42 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid;Reflux; | General procedure: General procedure for the preparation of 3 or 4-alkoxyphthalic anhydride (7a-7d, 9a-9d) Following a reported procedure [34], we added H2SO4 (0.054 mL, 1.02 mmol) to a stirred solution of 3- or 4-hydroxyphthalic acid (1.09 g, 6.00 mmol) in 12 mL of MeOH and the reaction was stirred at reflux overnight. Solvent was removed under reduced pressure and the solid residue obtained was dissolved in dichloromethane (40 mL) and washed with water (20 x 3 mL). The combined organic layer was dried over anhydr MgSO4, filtered and concentrated under reduced pressure to provide crude dimethyl 4-hydroxyphthalate. | |
With sulfuric acid;Reflux; | 3-Hydroxyphthalic acid (1.09 g, 6.0 mmol) was dissolved in 12 ml of methanol. H2SO4 (0.054 ml, 1.02 mmol) was added thereto as a catalyst. The reaction mixture was stirred under reflux for overnight. The solvent was eliminated under reduced pressure, and the obtained solid was dissolved in dichloromethane, which was washed with water. The combined organic layer was dried over MgSO4, and the solvent was eliminated under reduced pressure. As a result, a crude target compound was obtained (1.05 g, 83%). 1H NMR (DMSO-d6, 500 MHz) delta 10.31 (s, 1H), 7.41-7.35 (m, 2H), 7.17 (dd, J=7.0, 2.2 Hz, 1H), 3.79 (s, 3H), 3.77 (s, 3H). 13C NMR (DMSO-d6, 125 MHz) delta 167.2, 165.7, 154.6, 130.5, 128.6, 122.6, 120.5, 120.0, 52.4, 52.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: General procedure for the preparation of 3 or 4-alkoxyphthalic anhydride (7a-7d, 9a-9d) Following a reported procedure [34], we added H2SO4 (0.054 mL, 1.02 mmol) to a stirred solution of 3- or 4-hydroxyphthalic acid (1.09 g, 6.00 mmol) in 12 mL of MeOH and the reaction was stirred at reflux overnight. Solvent was removed under reduced pressure and the solid residue obtained was dissolved in dichloromethane (40 mL) and washed with water (20 x 3 mL). The combined organic layer was dried over anhydr MgSO4, filtered and concentrated under reduced pressure to provide crude dimethyl 4-hydroxyphthalate. The crude dimethyl 3- or 4-hydroxyphthalate was dissolved in 3 mL of acetone and K2CO3 (1.3 g, 9.5 mmol)was added to the solution. The mixture was stirred at room temperature for 1 h. Alkyl iodide (5.7 mmol) was added, and the mixture was stirred at reflux overnight. K2CO3 was removed by filtration and the solvent was removed under reduced pressure to provide dimethyl 3- or 4-alkoxyphthalate. | ||
0.49 g | The compound prepared in step 1 above (0.5 g, 2.38 mmol) was dissolved in 5 ml of acetone, followed by stirring in the presence of K2CO3 (1.64 g, 11.9 mmol) at room temperature for 1 hour. Iodoethane (0.57 ml, 7.13 mmol) was added thereto, followed by stirring under reflux for overnight. The reaction mixture was filtered to remove K2CO3 and the solvent was eliminated under reduced pressure. After evaporating the solvent, the obtained product was purified by flash column chromatography. As a result, a target compound was obtained (0.49 g, 87%). 1H NMR (DMSO-d6, 500 MHz) delta 7.56-7.49 (m, 2H), 7.39 (dd, J=7.6, 1.8 Hz, 1H), 4.10 (q, J=7.0 Hz, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 1.27 (t, J=7.0 Hz, 3H). 13C NMR (DMSO-d6, 125 MHz) delta 166.7, 165.2, 155.3, 130.8, 128.0, 124.9, 121.3, 117.5, 64.5, 52.6, 52.1, 14.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: General procedure for the preparation of 3 or 4-alkoxyphthalic anhydride (7a-7d, 9a-9d) Following a reported procedure [34], we added H2SO4 (0.054 mL, 1.02 mmol) to a stirred solution of 3- or 4-hydroxyphthalic acid (1.09 g, 6.00 mmol) in 12 mL of MeOH and the reaction was stirred at reflux overnight. Solvent was removed under reduced pressure and the solid residue obtained was dissolved in dichloromethane (40 mL) and washed with water (20 x 3 mL). The combined organic layer was dried over anhydr MgSO4, filtered and concentrated under reduced pressure to provide crude dimethyl 4-hydroxyphthalate. The crude dimethyl 3- or 4-hydroxyphthalate was dissolved in 3 mL of acetone and K2CO3 (1.3 g, 9.5 mmol)was added to the solution. The mixture was stirred at room temperature for 1 h. Alkyl iodide (5.7 mmol) was added, and the mixture was stirred at reflux overnight. K2CO3 was removed by filtration and the solvent was removed under reduced pressure to provide dimethyl 3- or 4-alkoxyphthalate. | ||
0.52 g | The compound prepared in step 1 above (0.5 g, 2.38 mmol) was dissolved in 5 ml of acetone, followed by stirring in the presence of K2CO3 (1.64 g, 11.9 mmol) at room temperature for 1 hour. Iodopropane (0.70 ml, 7.13 mmol) was added thereto, followed by stirring under reflux for overnight. The reaction mixture was filtered to remove K2CO3 and the solvent was eliminated under reduced pressure. After evaporating the solvent, the obtained product was purified by flash column chromatography. As a result, a target compound was obtained (0.52 g, 86%). 1H NMR (DMSO-d6, 500 MHz) delta 7.57-7.47 (m, 2H), 7.38 (dd, J=7.1, 2.3 Hz, 1H), 4.00 (t, J=6.3 Hz, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 1.76-1.59 (m, 2H), 0.93 (t, J=7.4 Hz, 3H). 13C NMR (DMSO-d6, 125 MHz) delta 166.7, 165.2, 155.4, 130.7, 127.9, 124.9, 121.2, 117.4, 70.0, 52.5, 52.1, 21.9, 10.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: General procedure for the preparation of 3 or 4-alkoxyphthalic anhydride (7a-7d, 9a-9d) Following a reported procedure [34], we added H2SO4 (0.054 mL, 1.02 mmol) to a stirred solution of 3- or 4-hydroxyphthalic acid (1.09 g, 6.00 mmol) in 12 mL of MeOH and the reaction was stirred at reflux overnight. Solvent was removed under reduced pressure and the solid residue obtained was dissolved in dichloromethane (40 mL) and washed with water (20 x 3 mL). The combined organic layer was dried over anhydr MgSO4, filtered and concentrated under reduced pressure to provide crude dimethyl 4-hydroxyphthalate. The crude dimethyl 3- or 4-hydroxyphthalate was dissolved in 3 mL of acetone and K2CO3 (1.3 g, 9.5 mmol)was added to the solution. The mixture was stirred at room temperature for 1 h. Alkyl iodide (5.7 mmol) was added, and the mixture was stirred at reflux overnight. K2CO3 was removed by filtration and the solvent was removed under reduced pressure to provide dimethyl 3- or 4-alkoxyphthalate. | ||
0.51 g | The compound prepared in step 1 above (0.5 g, 2.38 mmol) was dissolved in 5 ml of acetone, followed by stirring in the presence of K2CO3 (1.64 g, 11.9 mmol) at room temperature for 1 hour. Iodobutane (0.81 ml, 7.13 mmol) was added thereto, followed by stirring under reflux for overnight. The reaction mixture was filtered to remove K2CO3 and the solvent was eliminated under reduced pressure. After evaporating the solvent, the obtained product was purified by flash column chromatography. As a result, a target compound was obtained (0.51 g, 80%). 1H NMR (DMSO-d6, 500 MHz) delta 7.55-7.50 (m, 2H), 7.39 (dd, J=7.4, 1.9 Hz, 1H), 4.04 (t, J=6.3 Hz, 2H), 3.81 (s, 3H), 3.78 (s, 3H), 1.69-1.59 (m, 2H), 1.46-1.33 (m, 2H), 0.90 (t, J=7.4 Hz, 3H). 13C NMR (DMSO-d6, 125 MHz) delta 166.7, 165.2, 155.4, 130.7, 127.9, 124.9, 121.2, 117.4, 68.3, 52.5, 52.1, 30.5, 18.5, 13.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: General procedure for the preparation of 3 or 4-alkoxyphthalic anhydride (7a-7d, 9a-9d) Following a reported procedure [34], we added H2SO4 (0.054 mL, 1.02 mmol) to a stirred solution of 3- or 4-hydroxyphthalic acid (1.09 g, 6.00 mmol) in 12 mL of MeOH and the reaction was stirred at reflux overnight. Solvent was removed under reduced pressure and the solid residue obtained was dissolved in dichloromethane (40 mL) and washed with water (20 x 3 mL). The combined organic layer was dried over anhydr MgSO4, filtered and concentrated under reduced pressure to provide crude dimethyl 4-hydroxyphthalate. The crude dimethyl 3- or 4-hydroxyphthalate was dissolved in 3 mL of acetone and K2CO3 (1.3 g, 9.5 mmol)was added to the solution. The mixture was stirred at room temperature for 1 h. Alkyl iodide (5.7 mmol) was added, and the mixture was stirred at reflux overnight. K2CO3 was removed by filtration and the solvent was removed under reduced pressure to provide dimethyl 3- or 4-alkoxyphthalate. | ||
0.55 g | The compound prepared in step 1 above (0.50 g, 2.38 mmol) was dissolved in 5 ml of acetone, followed by stirring in the presence of K2CO3 (1.64 g, 11.9 mmol) at room temperature for 1 hour. Iodopentane (0.93 ml, 7.13 mmol) was added thereto, followed by stirring under reflux for overnight. The reaction mixture was filtered to remove K2CO3 and the solvent was eliminated under reduced pressure. After evaporating the solvent, the obtained product was purified by flash column chromatography. As a result, a target compound was obtained (0.55 g, 82%). 1H NMR (DMSO-d6, 500 MHz) delta 7.55-7.49 (m, 2H), 7.39 (d, J=7.4 Hz, 1H), 4.03 (t, J=6.2 Hz, 2H), 3.81 (s, 3H), 3.78 (s, 3H), 1.69-1.63 (m, 2H), 1.39-1.27 (m, 4H), 0.88 (t, J=6.9 Hz, 3H). 13C NMR (DMSO-d6, 125 MHz) delta 166.7, 165.2, 155.4, 130.7, 127.9, 124.9, 121.2, 117.4, 68.6, 52.5, 52.0, 28.1, 27.5, 21.7, 13.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 18h; | To a 0 C mixture of terf-butyl 7-hydroxyheptanoate (Preparation 22) (0.46 g, 2.27 mmol), triphenylphosphine (0.52 g, 2.0 mmol) and 1 ,2-dimethyl 3-hydroxybenzene-1 ,2- dicarboxylate (0.35 g, 1.67 mmol) in THF (3 mL), was added DIAD (0.39 mL, 2.00 mmol) dropwise. The mixture was stirred at r.t. for 18 hours. The solvent was removed in vacuo and the crude product was partitioned between EtOAc (20 mL) and water (20 mL). The organic phase was washed with brine, dried over MgS04 and the solvent was removed in vacuo. The crude product solubilised in 1 :1 THF:MeOH (24mL). NaOH (1 M aqueous solution, 5mL) was added and the resulting solution was stirred at r.t. for 2 hours. The mixture was then acidified to pH 4-5 with a 1 M HCI aqueous solution. The organic layer was extracted with EtOAc. The organic layers were combined, dried over MgS04 and the solvent was removed in vacuo. The crude product was purified by column chromatography using 1 :1 EtOAc: PE to give 3-[7-(terf-butoxy)-7-oxoheptyl]oxy}-2- (methoxycarbonyl)benzoic acid (0.47 g, 1.24 mmol, 75%) as a colourless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 96h; | To a 0 C mixture of 1 ,2-dimethyl 3-hydroxybenzene-1 ,2-dicarboxylate (0.15 g, 0.71 mmol), triphenylphosphine (0.23 g, 0.86 mmol) and te/Y-butyl 8-hydroxyoctanoate (Preparation 26) (0: 19 g, 0.86 mmol) in THF (1.2 mL), was added DIAD (0.17 mL, 0.86 mmol) dropwise. The mixture was stirred at room temperature for 4 days. The solvent was removed in vacuo and the crude product was partitioned between EtOAc (20 mL) and water (20 mL). The organic phase was washed with brine (20 mL), dried over MgS04 and the solvent was removed in vacuo. The crude product was purified by flash column chromatography with 1 : 4 EtOAc: Petrol to give 1 ,2-dimethyl 3-[8-(te/?-butoxy)-8-oxooctyl]oxy}benzene-1 ,2-dicarboxylate (0.24 g, 0.59 mmol, 82%) as colourless oil. Not pure after purification. 1H NMR (400 MHz, DMSO-cfe) delta ppm 7.57-7.47 (m, 2H), 7.40 (dd, J = 7.2, 2.0 Hz, 1 H), 4.07-4.04 (m, 2H), 3.82 (s, 3H), 3.78 (s, 3H), 2.18 (t, J = 7.3 Hz, 2H), 1.71-1.60 (m, 2H), 1.60-1.45 (m, 2H), 1.39 (s, 9H), 1.38-1.33 (m, 2H), 1.32-1.24 (m, 4H). LCMS: [M+H]+ = 409. |
Tags: 36669-02-0 synthesis path| 36669-02-0 SDS| 36669-02-0 COA| 36669-02-0 purity| 36669-02-0 application| 36669-02-0 NMR| 36669-02-0 COA| 36669-02-0 structure
[ 67609-51-2 ]
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P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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