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Structure of 1-Chloroethyl chloroformate
CAS No.: 50893-53-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 50893-53-3 |
Formula : | C3H4Cl2O2 |
M.W : | 142.97 |
SMILES Code : | O=C(Cl)OC(Cl)C |
MDL No. : | MFCD00000647 |
InChI Key : | QOPVNWQGBQYBBP-UHFFFAOYSA-N |
Pubchem ID : | 521305 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H226-H302-H314-H330 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P260-P264-P270-P271-P280-P284-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P363-P370+P378-P403+P233-P403+P235-P405-P501 |
Class: | 6.1(3,8) |
UN#: | 2742 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
97% | With pyridine In dichloromethane at 0 - 20℃; for 1.5 h; | To an ice cold reaction mixture containing p-nitrophenol (1.39 g, 10 mmol) and pyridine (0.81 g, 10 mmol) in dichloromethane (60 mL) was added 1-chloroethyl chloroformate (1.2 mL, 11 mmol). The mixture was stirred at 0° C. for 30 min and then at room temperature for 1 hour. After removing the solvent under reduced pressure, the residue was dissolved in ether, washed with water, 10percent citric acid and water. The ether layer was dried over Na2SO4 and evaporated under reduced pressure to give 2.4 g (97percent) of the title compound (57) as an off-white solid. 1H NMR (CDCl3): 1.93 (d, 3H), 6.55 (q, 1H), 7.42 (d, 2H), 8.28 (d, 2H). |
92% | With pyridine In dichloromethane at 0 - 20℃; for 6 h; | Example 3: 1-iodoethyl 4-nitrophenyl carbonateSTEP A: 1-chloroethyl 4-nitrophenyl carbonate.To a solution of 4-nitrophenol (3.0 g, 21.6 mmol) and pyridine (1.9 mL, 24 mmol) in CH2C12 (48 mL) cooled to 0°C, 1-chloroethyl chloroformate (2.3 mL, 21.6 mmol) was added. The reaction was stirred at room temperature for 5-6 hours, then washed with NaH2PC>4 (5percent) and brine, dried over Na2SC>4 and concentrated affording the title compound (4.88 g, 92percent) as a pale yellow solid. |
92% | at 0 - 20℃; | STEP A: 1-chloroethyl 4-nitrophenyl carbonateTo a solution of 4-nitrophenol (3.0 g, 21.6 mmol) and pyridine (1.9 mL, 24 mmol) cooled to 0°C, 1-chloroethyl chloroformate (2.3 mL, 21.6 mmol) was added. The reaction was stirred at room temperature for 5-6 hours, then washed with Na3/4P04 (5percent) and brine, dried over Na2 S C>4 and concentrated affording the title compound (4.88 g, 92percent) as a pale yellow solid.1H-NMR (CDC13) : 8.32 (2H,m); 7.44 (2H,m); 6.52 ( 1H, q, J=5.8 Hz); 1.94 (3H, d, J=5.5Hz) . |
88% | With pyridine In chloroform at 0 - 20℃; | Step 1: 1-Chloroethylchloroformate (7.8 ml, 72 mmol, 1 eq.) was added to an ice-cold solution of p-nitrophenol (10 g, 72 mmol) in chloroform (100 mL), followed by drop wise addition of pyridine (8.8 ml, 108 mmol, 1.5 eq.) over a period of 20 min. The mixture was stirred in the ice-cold bath for 15 min, and then at room temperature overnight. The reaction mixture was sequentially washed with water, 1 N hydrochloric acid, water, 1 N sodium hydroxide, water, and brine. The organic phase was dried over Na2SO4, and concentrated to give yellow oil which, upon standing, crystallized to afford the corresponding chloroethyl carbonate (15.5 g, 88percent). |
85% | With triethylamine In dichloromethane at 0 - 20℃; | To an ice-cold solution of 4-nitrophenol (2.0 g, 15 mmol) and triethylamine (1.6 g, 16 mmol) in dichloromethane (20 ml) was added a solution of 1-chloroethyl chloroformate (2.1 g, 19 mmol) in dichloromethane, and the mixture was stirred for 15 min at 0 °C and then overnight at room temperature. The mixture was extracted with dichloromethane (50 ml), washed successively with water (50 ml), 0.5 N sodium hydroxide (50 ml), saturated aqueous sodium chloride solution (50 ml), and water (3 x 50 ml), and dried over Na2SO4. The dichloromethane solution was filtered and evaporated under reduced pressure, and the residue was purified by silica gel column chromatography with chloroform (100percent) as eluent to furnish pure 1-chloroethyl 4- nitrophenyl carbonate, as a white solid in 85percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In tetrahydrofuran; at 0 - 20℃; for 24.0h; | A solution of 1-chloroethyl chloroformate (3.84 mL) in tetrahydrofuran (20 mL) was added dropwise to a solution of <strong>[4740-78-7]glycerol formal</strong> (2.92 mL) and pyridine (5.46 mL) in tetrahydrofuran (100 mL) at 0C. The mixture was stirred at room temperature for 24 hrs. and the precipitated solid was filtered off. Ethyl acetate (100 mL) was added to the filtrate and the mixture was washed with water (100 mL), 1N hydrochloric acid (100 mL) and saturated brine (100 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel flash column chromatography (eluted with ethyl acetate:hexane=1:40-1:10) to give the title compound (2.95 g) as a colorless oil.1H-NMR(CDCl3): 1.85(3H,d,J=6.0Hz), 4.04(4H,t,J=3.0Hz), 4.66(1H,quintet,J=3.0Hz), 4.81(1H,d,J=6.0Hz), 4.95(1H,d,J=6.0Hz), 6.42(1H,q,J=6.0Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,2-dichloro-ethane; at 0℃; for 16h;Heating / reflux; | To a stirring solution OF TROPINONE (LOG, 72MMOL) into 350ML DCE at 0°C was added 1-chloroethyl chloroformate (11. 6ML, 108MMOL). The reaction mixture was then heated to reflux and stirred for 16 hours. Upon completion (TLC), volatiles were removed in vacuo and the dark brown residue was washed with ether and filtered. The filtrate was concentrated under reduced pressure and the product formed a brown oil (Yield: 12.65g, 54. 7MMOL). The brown oil was dissolved in 100mL MEOH and set to reflux for 2 hours. Upon completion (TLC), the methanol was removed in vacuo and the residue was dissolved in ether. Solid particulates were filtered, and the ether was removed under reduced pressure and 8-aza-bicyclo [3.2. 1] octan-3-one hydrochloride formed as a beige solid (Yield: 5. 0g, 40mmol). The product was used without any further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium chloride; triethylamine; In methanol; dichloromethane; | Methyl 1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydro-4-pyridinecarboxylate 4.62 g of <strong>[80845-58-5]methyl 1-benzyl-1,2,3,6-tetrahydro-4-pyridinecarboxylate</strong> was dissolved in 30 ml of dichloromethane. Under ice-cooling, 4.29 g of 1-chloroethyl chloroformate was added thereto and the resulting mixture was heated under reflux for 2 hours. After adding 50 ml of methanol, the mixture was stirred at 70 C. for 1 hour and 20 minutes. Then triethylamine was added to the reaction mixture under ice-cooling until the pH value of the mixture exceeded 7. After further adding 4.37 g of tert-butyl dicarbonate, the resulting mixture was stirred at room temperature for 10 minutes. Then the reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed successively with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 4.46 g of the title compound as a yellow oily substance. 1H-NMR(CDCl3) delta ppm: 1.47(s, 9H), 2.40(br.s, 2H), 3.51(t, J=5.6 Hz, 2H), 3.76(s, 3H), 4.07(d, J=2.4 Hz, 2H), 6.88(br.s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With calcium carbonate; In 1,4-dioxane; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; | Step 2 2-chloroethyl-N-[(4-fluoro-2-methyl-5-nitro)phenyl]-carbamate 5 g (29 mmol) of <strong>[446-18-4]2-amino-5-fluoro-4-nitrotoluene</strong> was heated with 2.5 g calcium carbonate in 200 ml dioxan at 70 C., reacted with 3.1 ml of chloroformic acid chloroethyl ester and heated for 3 hours at 100 C. The resultant solution was filtered hot and the filtrate is introduced into 500 ml of ice water. The ocher colored precipitate was filtered with suction and recrystallized from an ethanol-water mixture. The resulting 6.6 g (81% of theoretical) of 2-chloroethyl-N-[(4-fluoro-2-methyl-5-nitro)phenyl]-carbamate had a melting point of 113 C. 1 H-NMR(D6 -DMSO): delta=2.33 (s; 3H, --CH3) 3.88 (t; 2H, --CH2 Cl) 4.38 (t; 2H, --CH2 CH2 Cl) 7.49 (d, J=12.3 Hz; 1H, 6-H) 8.22 (d, J=7.3 Hz; 1H, 3-H) 9.44 (br.s; 2H, --NH, exchange with D2 O) MS(70ev): m/e=276(M+.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
[0165] To a stirred solution of the benzyl amine (32) (10 g, 1 equiv.) in dichloroethane (220 mL) was added, dropwise, 1-chloroethylchloroformate (5.91 mL, 1.2 equiv.). The reaction was stirred at rt for 30 min followed by concentration of the mixture under reduced pressure. The residue was dissolved in MeOH (100 mL), refluxed for 20 min and then concentrated under reduced pressure. The residue was then dissolved in CHCl3 (80 mL) and Et3N (19.1 mL, 3 equiv.) and cooled to 0 C. To this mixture was added Boc2O (9.95 g, 1 equiv.) in CHCl3 (20 mL) and the reaction was stirred at rt for 16 h. This mixture was then concentrated under reduced pressure, dissolved in EtOAc and washed with 10% citric acid, H2O and brine. The organic extract was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution: 20% EtOAc in hexane to 33% EtOAc in hexane) to afford the Boc-protected amine. To a solution of the Boc-protected amine (2.29 g, 1 equiv.) in MeOH (24 mL) was added 1 N NaOH (12 mL, 1.2 equiv.). The mixture was stirred at rt for 3 days and then concentrated under reduced pressure. The residue was poured into a solution of 1 N HCl (10 mL) and 10% citric acid (20 mL). The mixture was extracted with EtOAc (3×) and the combined organic extracts were washed with H2O and brine, dried (MgSO4) and concentrated under reduced pressure to yield the acid (33). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of <strong>[105601-04-5]3-[1-(dimethylamino)ethyl]phenol</strong> (0.41 g, 2.5 mmoL) and triethylamine (0.8 g, 7.9 mmoL) in dichloromethane (10 mL) was stirred under nitrogen and cooled using an ice-bath. 1-Chloroethyl chloroformate (0.43 g, 3 mmoL) was added to the solution and the mixture was stirred for 1 h whereupon N-ethylmethylamine (0.24 g, 4 mmoL) was added and the solution was allowed to warm slowly to room temperature and stirred overnight. The reaction mixture was quenched by the addition of water (10 mL) and the pH of the aqueous layer was adjusted to >10 by the addition of aqueous NaOH solution. The organic layer was separated and the aqueous layer was extracted with additional dichloromethane. The combined organic extracts were washed with water and evaporated to dryness. The residue was dissolved in diethyl ether and extracted with dilute HCl solution. The pH of the aqueous solution was adjusted to >10 by the addition of aqueous NaOH solution and extracted with diethyl ether. The ethereal layers were washed with water and then evaporated to dryness to give racemic Rivastigime (0.5 g) as a liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
184.7 g | Example 1 <strong>[132335-47-8](S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propanamine oxalate</strong> (204g, 0.508mol) added to a flask, afterwhich 1L of toluene was added, followed by 1L of water, and stirred, then was added with 200g K2CO3, stirred for 30 min, until the solid was completely dissolved, the layers were then separated, toluene layer was washed once with 500mL water, 500mL brine, dried with MgSO4, and filtered, afterwhich the toluene layer was added with N,N-diisopropylethylamine (6.5g, 0.0508mol) and stirred, followed by dropwise addition of 1-chloroethyl chloroformate (87.2g, 0.61) while maintaining the reaction temperature at 35C-45C, stirred for 3 hrs, complete conversion of the reaction was monitored through TLC, then cooled to 20C, then washed with 500mL 5% NaOH aqueous solution, the toluene layer was washed with 5% hydrochloric acid and 500mL 5% NaHCO3 once, washed with 500mL brine once, concentrated under reduced pressure to 55 deg. C, toluene-free fraction was taken to give 1-chloroethyl-N-methyl-((S)-3-(naphthalene-1-yloxy)-3-(thiophen-2-yl)propyl)carbamate (184.7g, 0.46mol). 1L THF was then added, followed by addition of 1L of water with stirring, followed by addition of KOH (57g, 1.1mol) with stirring, warmed to 55C, heated for 4h, TLC monitored completion of the reaction, at 50C concentrated under reduced pressure to a non-flowing THF, cooled to 20C, then extracted with 1L of toluene. Duloxetine in toluene solution was added oxalic acid-ethanol solution (oxalate dihydrate 64g / 128g ethanol), stirred, filtered, and added to 1.2 L of ethyl acetate, water, 259g K2CO3, mixed and stirred. The ethyl acetate layer was separated and added with 29.5g of concentrated hydrochloric acid, stirred and filtered to give 100.7 g of duloxetine hydrochloride, from (S)-N,N-dimethyl-3- (1-naphthyloxy)-3-(2-thienyl)propanamine oxalate, total yield 59.4%, optical purity 99.9%, 99.8% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.15 g | With triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | In a round bottom flask, Compound 1 (t-Boc-NHCH2CH2NHCH2CH3; 1.50 g) was dissolved in anhydrous dichloromethane (60 ml) and the solution was cooled to 0-5 C. Triethylamine (TEA, 1.2 ml) was added followed by 1-chloroethyl chloroformate (0.79 ml) and the mixture was stirred for three hours at room temperature. Next, the mixture was washed with 0.1M solution of NaH2PO4 (50 ml and 30 ml) and dried with anhydrous MgSO4. Then, the solvent was distilled under reduced pressure giving 2.15 g of the desired product. |
Tags: 50893-53-3 synthesis path| 50893-53-3 SDS| 50893-53-3 COA| 50893-53-3 purity| 50893-53-3 application| 50893-53-3 NMR| 50893-53-3 COA| 50893-53-3 structure
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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 |
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