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CAS No. : | 2199-43-1 | MDL No. : | MFCD00817049 |
Formula : | C7H9NO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | PAEYAKGINDQUCT-UHFFFAOYSA-N |
M.W : | 139.15 | Pubchem ID : | 255670 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | 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 |
---|---|---|
82% | With aluminum (III) chloride; In nitromethane; dichloromethane; at -20℃; for 2h; | To a solution of Compound 115 (5 g, 35.9 mmol) and aluminum chloride (11.5 g, 86.0 mmol) in methylene chloride/nitromethane (1:1, 150 mL) was added dropwise dichloro methoxymethane (116)(3.8 mL, 43.1 mmol) at -20 C over 30 minutes. The reaction mixture was stirred for 1.5 hours and poured to ice water and extracted with methylene chloride. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The obtained brown residue was recrystallized from hexane/ethyl acetate to give a light brown Compound 117 (4.95 g, Yield 82 %). 1H NMR (DMSO-d6) δ: 1.29 (t, J = 6.9 Hz, 3H), 4.27 (q, J = 6.9 Hz, 2H), 7.11 (d, J = 0.15 Hz, 1H), 7.81 (d, J = 1.8 Hz, 1H), 9.75 (s, 1H), 12.7 (brs, 1H). |
54% | With aluminum (III) chloride; In nitromethane; 1,2-dichloro-ethane; at -20℃; | Ethyl pyrrole-2-carboxylate (6.9 g, 49.6 mmol) and aluminum trichloride (13.2 g, 99.2 mmol) were added to 1,2-dichloroethane-nitromethane (1:1, 100 mL), The temperature was lowered to -20C, dichloro(methoxy)methane (11.4 g, 99.2 mmol) was added dropwise, stirring was continued for 1 hour, and it was allowed to stand at -20C overnight.The reaction solution was poured into 100 mL of ice water, the organic phase was separated, the aqueous layer was extracted with DCM (3×100 mL), washed with ammonia water (200 mL), dried over sodium sulfate, concentrated under reduced pressure, and the crude product was subjected to silica gel column chromatography (petroleum ether:ethyl acetate) =1:1) 5.0 g of yellow solid ethyl 4-formyl-1H-pyrrole-2-carboxylate was obtained with a yield of 54% |
With aluminum (III) chloride; In nitromethane; dichloromethane; at -10 - 20℃; for 18h; | Add anhydrous dichloromethane (5L) into a dry 10L three-neck flask, start stirring,Compound 1-SMA (500.00g) and nitromethane were added to a three-necked flask in sequence, and the system was placed in a dry ice ethanol bath, and the temperature was cooled to -10C.Control the temperature -10~0, slowly add aluminum trichloride (1.15kg) into the reaction flask, control the temperature below 0, add α,α-dichlorodimethyl methyl ether (495.00g) slowly Slowly rise to room temperature in the reaction kettle and stir for 18 hours.TLC (PE:EA 3:1) monitoring shows that the raw material point disappears and a new point with high polarity is formed.Withdraw the reaction solution, slowly add dropwise to 10% potassium hydrogen sulfate solution (3L), stir for 20 minutes, add crushed ice to prevent overheating.The mixed solution was transferred to a 25L separatory funnel, allowed to stand and separate to separate the dichloromethane layer, and the aqueous phase was extracted with dichloromethane (2L*2).The organic phase was washed with 10% potassium hydrogen sulfate solution (5L*2), the organic phase was separated and dried with anhydrous sodium sulfate (1kg).The organic phase is concentrated under reduced pressure,The dark green solid compound 1-A was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50%; 7% | A-6 5-Formyl-1H-pyrrole-2-carboxylic acid To a solution of dimethylformamide (21 mL, 0.27 mol) in 75 mL of dichloroethane was added a solution of phosphorus oxychloride (25 mL, 0.27 mol) in 75 mL of dichloroethane at 0 oC. The mixture was stirred at room temperature for 30 minutes and cooled to 0 oC. To the mixture was added a solution of ethyl pyrrole-2-carboxylate (25 g, 0.18 mol) in 50 mL of dichloroethane dropwise. The resulting mixture was stirred at room temperature for 30 minutes and then at 40 oC for 1 hour. The mixture was poured into ice and basified to pH 11 with 5 N sodium hydroxide solution. The mixture was extracted with ethyl acetate and the extract washed with water and brine and dried over anhydrous sodium sulfate. The two products were separated by column chromatography (1:3 ethyl acetate:hexane) to give 15 g (50% yield) of 5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester and 2 g (7% yield) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester. 1H-NMR (300 MHz, dimethylsulfoxide) δ 13.02 (br s, 1H, NH), 9.69 (s, 1H, CHO), 6.95 (d, 1H), 6.86 (d, 1H), 4.27 (q, 2H, CH3), 1.28 (t, 3H, CH3). MS m/z 167 [M+]. | |
50%; 7% | To a solution of dimethylformamide (21 mL, 0.27 mol) in 75 mL of dichloroethane was added a solution of phosphorus oxychloride (25 mL, 0.27 mol) in 75 mL of dichloroethane at 0 oC. The mixture was stirred at room temperature for 30 minutes and cooled to 0 oC. To the mixture was added a solution of ethyl pyrrole-2-carboxylate (25 g, 0.18 mol) in 50 mL of dichloroethane dropwise. The resulting mixture was stirred at room temperature for 30 minutes and then at 40 oC. for 1 hour. The mixture was poured into ice and basified to pH 11 with 5 N sodium hydroxide solution. The mixture was extracted with ethyl acetate and the extract washed with water, brine and dried over anhydrous sodium sulfate. The two products were separated by column chromatography (1:3 ethyl acetate:hexane) to give 15 g (50% yield) of 5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester and 2 g (7% yield) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester. 1H-NMR (5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester) (300 MHz, dimethylsulfoxide) δ 13.02 (br s, 1H, NH), 9.69 (s, 1H, CHO), 6.95 (d, 1H), 6.86 (d, 1H), 4.27 (q, 2H, CH3), 1.28 (t, 3H, CH3). MS m/z 167 [M+]. | |
50%; 7% | [0179] To a solution of dimethylformamide (21 mL, 0.27 mol) in 75 mL of dichloroethane was added a solution of phosphorus oxychloride (25 mL, 0.27 mol) in 75 mL of dichloroethane at 0 C. The mixture was stirred at room temperature for 30 minutes and cooled to 0 C. To the mixture was added a solution of ethyl pyrrole-2-carboxylate (25 g, 0.18 mol) in 50 mL of dichloroethane dropwise. The resulting mixture was stirred at room temperature for 30 minutes and then at 40 C. for 1 hour. The mixture was poured into ice and basified to pH 11 with 5 N sodium hydroxide solution. The mixture was extracted with ethyl acetate and the extract washed with water and brine and dried over anhydrous sodium sulfate. The two products were separated by column chromatography (1:3 ethyl acetate:hexane) to give 15 g (50% yield) of 5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester and 2 g (7% yield) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester. 1H-NMR (300 MHz, dimethylsulfoxide) δ 13.02 (br s, 1H, NH), 9.69 (s, 1H, CHO), 6.95 (d, 1H), 6.86 (d, 1H), 4.27 (q, 2H, CH3), 1.28 (t, 3H, CH3). MS M/Z 167 [M+]. |
46%; 42% | With trichlorophosphate; at 30℃;Inert atmosphere; Cooling with ice; | To an ice-cooled solution of ethyl 1H-pyrrole-2-carboxylate2 (10 g, 72 mmol) in dry DMF (129.3 mL), freshly distilled phosphorus oxychloride (POCl3, 20.1 mL, 216 mmol) was added dropwise under argon atmosphere. After the completion of the addition, the cooling bath was removed and the reaction mixture was stirredat 30 C for 21 h. Then, the mixture was gradually added to ice-water, the pH was adjusted to pH=7 with 25 % aq. NH3 and the aqueous solution was extracted with DCM (3×). The combined organic layers were washed with saturated aqueous NaHCO3 (1×) and brine (1×), dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The resulting oily residue was purified by silica gel flash column chromatography (DCM/MeOH 98:2) to afford 4 (5 g, red-browns olid, 42 %) and ethyl 5-formyl-1H-pyrrole-2-carboxylate (5.5 g, red-brown solid, 46 %).For compound 4: Rf (toluene/EtOAc 8:2) 0.13. mp 103-104 C. IR (KBr): max 3175, 2881, 1705, 1651, 1269 cm-1. 1H NMR (CDCl3, 400 MHz): 10.10 (br s, 1H), 9.85 (s, 1H), 7.58 (dd, J = 3.3 Hz,J = 1.5 Hz, 1H), 7.33-7.32 (m, 1H), 4.36 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz,3H). 13C NMR (CDCl3, 100 MHz): 185.82, 161.12, 128.61, 127.69, 125.26, 114.28,61.31, 14.45. MS (ESI+) (m/z): 168.53 [M+H]+. HRMS-ESI (m/z): [M+Na]+ calcd for C8H9NO3: 190.04746, found: 109.04756. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53.6% | Ethylpyrrole-2-carboxylate (2.0589 g, 14.80 mmol) in a minimal amount of dichloroethane was added to an ice cooled stirring mixture of aluminum chloride (3.9913 g, 29.93 mmol) and 4-fluorophenylacetyl chloride (5.1338 g, 29.75 mmol) in dichloroethane (22 mL, 0.66 M) under N2. The ice bath was removed, and the reaction was stirred at room temperature for 3.5 h. 20.6195 g (2.6 mMol/g) Polyamine resin HL (200-400 mesh) and dichloroethane (20 mL) were added, and the reaction was stirred for 60 min. The reaction was then filtered through a glass-fritted funnel directly into ice water. The resin was rinsed with CH2Cl2, then the organic layers were removed, dried with Na2SO4, filtered and concentrated. When 6.5 mL of 80:20 Hexanes:EtOAc were added, the organic liquid turned yellow, leaving behind a tan solid. The solid was removed by filtration, rinsed with 80:20 Hexanes:EtOAc, and dried to obtain pure 71 (2.1838 g, 53.6%). 1H (CDCl3, 400 MHz): δ 10.03 (1H, broad s), 7.54 (1H, s), 7.32 (1H, s), 7.23 (2H, dd, J=8.6, 5.3 Hz), 6.99 (2H, t, J=8.6 Hz), 4.35 (2H, q, J=7.1 Hz), 4.04 (2H, s), 1.37 (3H, t, J=7.1 Hz) ppm. 13C (CDCl3, 100 MHz): δ 192.81, 161.84 (d, J=244 Hz), 160.95, 130.89 (d, J=7.8 Hz), 130.37 (d, J=3.2 Hz), 126.72, 126.36, 124.30, 115.40 (d, J=21.4 Hz), 114.96, 61.02, 45.63, 14.29 ppm. DEPT (CDCl3, 100 MHz): CH3 carbons: 14.29; CH2 carbons: 61.02, 45.63; CH carbons: 130.89 (d, J=7.8 Hz), 126.72, 115.40 (d, J=21.4 Hz), 114.96 ppm. HPLC: 9.689 min. |
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