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Ethylparaben, a natural product isolated and purified from the male melon fly Dacus cucurbitae, is the ethyl ester of p-hydroxybenzoic acid, used as an antifungal preservative.
Synonyms: Ethyl parahydroxybenzoate; Ethyl 4-hydroxybenzoate; NSC 23514
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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 120-47-8 |
Formula : | C9H10O3 |
M.W : | 166.17 |
SMILES Code : | O=C(OCC)C1=CC=C(O)C=C1 |
Synonyms : |
Ethyl parahydroxybenzoate; Ethyl 4-hydroxybenzoate; NSC 23514
|
MDL No. : | MFCD00002353 |
InChI Key : | NUVBSKCKDOMJSU-UHFFFAOYSA-N |
Pubchem ID : | 8434 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
85.6% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 20℃; for 24.0h; | Step 1 To a solution of DEAD (12.3 mL, 27.08 mmol)(40% in toluene)was added to a mixture of ethyl 4-hydroxybenzoate (XIII)(3.0 g, 18.05 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (XI)(4.72 g, 23.47 mmol)and triphenylphosphane (6.16 g, 23.47 mmol)in THF (40 mL)at 0 C. The mixture was stirred from 0 C. to room temperature over 1 day before concentrating in vacuo. The residue was diluted with EtOAc, washed with 1 N NaOH and brine, and then evaporated under vacuum. The crude product was purified by chromatography (0→30% EtOAc/hexanes)to give tert-butyl 4-(4-ethoxycarbonylphenoxy)piperidine-1-carboxylate (XIV)(5.4 g, 15.45 mmol, 85.6% yield)as a colorless oil. ESIMS found for C19H27NO5 m/z 372.1 (M+Na). |
85.6% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 24.0h; | To a solution of DEAD (12.3 mL, 27.08 mmol) (40% in toluene) was added to a mixture of ethyl 4-hydroxybenzoate (CXI) (3.0 g, 18.05 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (CIX) (4.72 g, 23.47 mmol) and triphenylphosphane (6.16 g, 23.47 mmol) in THF (40 mL) at 0 C. The mixture was stirred from 0 C. to room temperature over 1 day before concentrating in vacuo. The residue was diluted with EtOAc, washed with 1 N NaOH and brine, and then evaporated under vacuum. The crude product was purified by chromatography (0→30% EtOAc/hexanes) to give tert-butyl 4-(4-ethoxycarbonylphenoxy)piperidine-1-carboxylate (CXII) (5.4 g, 15.45 mmol, 85.6% yield) as a colorless oil. ESIMS found for C19H27NO5 m/z 372.1 (M+Na). |
85.6% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 20℃; for 24.0h; | To a solution of DEAD (12.3 mL, 27.08 mmol) (40% in toluene) was added to a mixture of ethyl 4-hydroxybenzoate (XXXV) (3.0 g, 18.05 mmol), tert-butyl 4-hydroxypiperidine-1-carboxylate (XXXVI) (4.72 g, 23.47 mmol) and triphenylphosphane (6.16 g, 23.47 mmol) in THF (40 mL) at 0 C. The mixture was stirred from 0 C. to room temperature over 1 day before concentrating in vacuo. The residue was diluted with EtOAc, washed with 1 N NaOH and brine, and then evaporated under vacuum. The crude product was purified by chromatography (0→30% EtOAc/hexanes) to give tert-butyl 4-(4-ethoxycarbonylphenoxy)piperidine-1-carboxylate (XXXVII) (5.4 g, 15.45 mmol, 85.6% yield) as a colorless oil. ESIMS found for C19H27NO5 m/z 372.1 (M+Na). |
62% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0℃; for 24.0h; | Reference Example 1:4-[(1-Cyclopentyl-4-piperidinyl)oxy]benzaldehyde (1) Production of tert-butyl 4-[4-(ethoxycarbonyl)phenoxy]tetrahydro-1(2H)-pyridinecarboxylate: Ethyl 4-hydroxybenzoate (4.15 g, 25.0 mmol), tert-butyl 4-hydroxytetrahydro-1(2H)-pyridinecarboxylate (5.0 g, 25.0 mmol) and triphenyl phosphine (7.87 g, 30.0 mmol) were dissolved in tetrahydrofuran (50 mL), and with stirring at 0C, diisopropyl azodicarboxylate (6.06 g, 30.0 mmol) was added thereto and stirred for 24 hours. The reaction solution was concentrated, and the precipitated white solid was taken out through filtration and washed with ethyl acetate. The mother liquid was washed with aqueous 1 N sodium hydroxide solution and saturated saline water in that order, and the organic layer was dried with magnesium sulfate. The solvent was evaporated off, and the residue was purified through silica gel column chromatography (hexane/ethyl acetate = 9/1) to obtain the intended compound (5.45 g, 62 %) as a colorless solid. |
39% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 16.0h; | Step A: tert-Butyl-4-(4-carboxyethylphenyloxy)- 1 -piperidinecarboxylateTo a pre-cooled (00C) suspension of ethyl 4-hydroxybenzoate (10.0 g, 60.2, mmol), 1- tert-butoxycarconyl 4-hydroxypiperidine (12.1 g, 60.1 mmol), and triphenylphosphine (15.8 g, 60.2 mmol) in THF is added diisopropyl azodocarboxylate (11.6 g, 60.1 mmol).The mixture is allowed to come to rt, stirred for 16 h, diluted with ethyl acetate, washed with water, sodium bicarbonate (saturated, aqueous), dried over sodium sulfate, filtered and evaporated in vacuo. The crude product is purified on silica to give the desired product (8.27 g, 39 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 6h; | 4-[4-(1,3-Dioxo-1 , 3-dihydro-isoindol-2-yl)-cyclohexyloxy]-benzoic acid ethyl ester; <n="63"/>To a stirred solution of 2-(4-hydroxycyclohexyl)isoindole-1 ,3-dione (8.0 g, 32.6 mmol) in dry THF (100 ml.) was added triphenyl phosphine (12.8 g, 48.8 mmol) and 4- hydroxy benzoic acid ethyl ester (5.44 g, 32.7 mmol). The reaction mixture was cooled to 0 0C and DIAD (9.6 g, 47.4 mmol) was added dropwise from an addition funnel over a period of 3 h. The reaction was gradually brought to room temperature and stirring continued for 3 h. The solvent was removed under vacuum and ether (100 ml.) was added and cooled to 0 0C. The solid formed was filtered and the clear filtrate concentrated and purified by column chromatography over neutral alumina (8 % AcOEt in hexane) to give 5.13 g (42 %) of 4-[4- (I .S-dioxo-I .S-dihydro-isoindol^-ylJ-cyclohexyloxyJ-benzoic acid ethyl ester. 1H-NMR (300 MHz, CDCI3); delta 1.24 - 1.36 (m, 2H), 1.40 (t, 3H), 1.63 - 1.77 (m, 3H), 2.19 - 2.29 (m, 2H), 2.62 - 2.79 (dq, 2H), 4.15 - 4.72 (m, 1 H), 4.35 (q, 2H), 7.01 (d, 2H), 7.71 (m, 2H), 7.82 (m, 2H), 8.0 (d, 2H). m/z: 394.1 (M+1 )+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; In tetrahydrofuran; ethyl acetate; | Step 1 Synthesis of ethyl 4-(1-t-butoxycarbonyl-4-piperidyloxy)benzoate: 1.7 g (10.2 mmol) of ethyl 4-hydroxybenzoate, 1.76 g (9.3 mmol) of 1-t-butoxycarbonyl-4-hydroxypiperidine, obtained by t-butoxycarbonylating 4-hydroxypiperidine with di-t-butyl dicarbonate in an ordinary manner, and 2.44 g (9.3 mmol) of triphenylphosphine were dissolved in 40 ml of tetrahydrofuran. 1.62 g (9.3 mmol) of diethyl azodicarboxylate was added to the obtained solution at room temperature, and they were stirred overnight. After the treatment with ethyl acetate as the extraction solvent in an ordinary manner, the crude product was obtained. It was purified by the silica gel column chromatography to obtain the title compound. Yield: 1.57 g (4.5 mmol) (44%) H-NMR (CDCl3) d δ 1.38 (3H, t), 1.50 (9H, s)1.70-1.80 (2H, m), 1.90-2.00 (2H, m), 3.30-3.41 (2H, m), 3.63-3.75 (2H, m), 4.35 (2H, q), 4.55 (1H, m), 6.90 (2H, d), 8.00 (2H, d) | |
With triphenylphosphine; In tetrahydrofuran; ethyl acetate; | Step 1 Synthesis of ethyl 4-(1-t-butoxycarbonyl-4-piperidyloxy)benzoate: 1.76 g (9.3 mmol) of 1-t-butoxycarbonyl-4-hydroxypiperidine, obtained by t-butoxycarbonylating 4-hydroxypiperidine with di-t-butyl dicarbonate by an ordinary method, 1.7 g (10.2 mmol) of ethyl 4-hydroxybenzoate and 2.44 g (9.3 mmol) of triphenylphosphine were dissolved in 40 ml of tetrahydrofuran. 1.62 g (9.3 mmol) of diethyl azodicarboxylate was added to the solution at room temperature and the resultant mixture was stirred overnight. The reaction mixture was treated with ethyl acetate as the extractant in an ordinary manner to obtain a crude product, which was purified by the silica gel column chromatography to obtain the title compound. Yield: 1.57 g (4.5 mmol) (44 %) H-NMR (CDCl3) δ 1.38 (3H, t), 1.50 (9H, s), 1.70-1.80 (2H, m), 1.90-2.00 (2H, m), 3.30-3.41 (2H, m), 3.63-3.75 (2H, m), 4.35 (2H, q), 4.55 (1H, m), 6.90 (2H, d), 8.00 (2H, d). | |
With triphenylphosphine; In tetrahydrofuran; ethyl acetate; | Step 1: Synthesis of ethyl 4-(1-t-butoxycarbonyl-4-piperidyloxy)benzoate: 1.76 g (93 mmol) of 1-t-butoxycarbonyl-4-hydroxypiperidine, obtained by t-butoxycarbonylating 4-hydroxypiperidine with di-t-butyl dicarbonate, 1.7 g (10.2 mmol) of ethyl 4-hydroxybenzoate and 2.44 g (9.3 mmol) of triphenylphosphine were dissolved in 40 ml of tetrahydrofuran. 1.62 g (9.3 mmol) of diethyl azodicarboxylate was added to the obtained solution, and they were stirred overnight. The reaction mixture was treated with ethyl acetate as the extraction solvent in an ordinary manner to obtain the crude product, which was purified by the silica gel column chromatography to obtain the title compound. Yield: 1.57 g (4.5 mmol) (44 %) H-NMR (CDCl3) δ 1.38 (3H, t), 1.50 (9H, s)1.70-1.80 (2H, m), 1.90-2.00 (2H, m), 3.30-3.41 (2H, m), 3.63-3.75 (2H, m), 4.35 (2H, q), 4.55 (1H, m), 6.90 (2H, d), 8.00 (2H, d) |
With triphenylphosphine; In tetrahydrofuran; | Step 1 Synthesis of ethyl 4-(1-t-butoxycarbonyl-4-piperidyloxy)benzoate: 1.7 g (10.2 mmol) of ethyl 4-hydroxybenzoate, 1.76 g (9.3 mmol) of 1-t-butoxycarbonyl-4-hydroxypiperidine and 2.44 g (9.3 mmol) of triphenylphosphine were dissolved in 40 ml of tetrahydrofuran. 1.62 g (9.3 mmol) of diethyl azodicarboxylate was added to the solution at room temperature, and they were stirred overnight. The crude product was obtained by the same isolation process as that of step 1 in Example 1 with ethyl acetate as the extractant. After the purification by the silica gel column chromatography, the title compound was obtained. Yield: 1.57 g (4.5 mmol) (44%) H-NMR (CDCl3) δ 1.38 (3H, t), 1.50 (9H, s)1.70-1.80 (2H, m), 1.90-2.00 (2H, m), 3.30-3.41 (2H, m), 3.63-3.75 (2H, m), 4.35(2H, q), 4.55(1H, m),6.90 (2H, d), 8.00 (2H, d) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 23℃; for 16h;Inert atmosphere; | A 100-mE round-bottom flask with a nitrogen ball was charged with piperidin-4-ol (1 g, 9.89 mmol), triphenylphosphine (3.5 g, 13.34 mmol), ethyl 4-hydroxybenzoate (2.25 g, 13.5 mmol), tetrahydroffiran (50 mE) and diethyl azodicarboxylate (3.45 g, 19.8 mmol). The resulting solution was stirred 16 h at 23° C. and concentrated under vacuum. The residue was purified by column chromatography eluting with ethyl acetate/petroleum ether (1:1 v/v) to afford ethyl 4-(1 -methylpyrrolidin-3-yloxy)benzoate (0.5 g, 20percent). ECMS: (ESI) mlz 250 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.34% | With potassium carbonate; In acetone; for 4h;Reflux; | General procedure: To a solution of various substituted phenols (1 mmol) in dry acetone (30 mL) K2CO3 (1 mmol)and compound 3 or 4 (1 mmol) were added. After being stirred for 4 h at reflux temperature, thereaction mixture was cooled, filtered, and concentrated under vacuum. Then the residue was dilutedwith 30 mL ethyl acetate and sequentially washed with 30 mL 1 M HCl, aq. NaHCO3 solution andbrine in order. The organic layer was dried over MgSO4 and concentrated in vacuo. Purification of theresidue by chromatography on silica gel furnished target compounds. 1H-NMR, 13C-NMR and massspectroscopy (MS) of compounds 5a-m and 6a-m are shown in Supplementary Materials. |
Tags: 120-47-8 synthesis path| 120-47-8 SDS| 120-47-8 COA| 120-47-8 purity| 120-47-8 application| 120-47-8 NMR| 120-47-8 COA| 120-47-8 structure
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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 |
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