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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. : | 122-98-5 |
Formula : | C8H11NO |
M.W : | 137.18 |
SMILES Code : | OCCNC1=CC=CC=C1 |
MDL No. : | MFCD00002832 |
InChI Key : | MWGATWIBSKHFMR-UHFFFAOYSA-N |
Pubchem ID : | 31235 |
GHS Pictogram: |
![]() |
Signal Word: | Danger |
Hazard Statements: | H310-H303-H315-H319 |
Precautionary Statements: | P501-P270-P262-P264-P280-P312-P337+P313-P305+P351+P338-P361+P364-P332+P313-P302+P352+P310-P405 |
Class: | 6.1 |
UN#: | 2810 |
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 |
---|---|---|
89% | With sodium hydroxide; In ethanol; water; at 0 - 38℃; for 2h;pH 12 - 12.5; | A500 mL flask was charged with 2-anilinoethanol (27.4 g, 180.1 mmol), 30 mLEtOH, an overhead stirrer, a calibrated pH probe, and 100 ml water. An additionfunnel was charged with 10 N sodium hydroxide solution (120 ml, 120.0 mmol).The solution was heated to 38 C, and treated with chloracetyl chloride (47.7ml, 600.0 mmol) via a syringe pump over 1 h. The sodium hydroxide solution wassimultaneously added to the stirring solution so that the pH was maintainedbetween 12 and 12.5. After the addition was complete, the solution was cooledto 0 C and stirred for 1 h. The solids were collected and washed with coldwate (2 × 60 mL). The solids were dried at 50 0C at 0.2 mm Hg for 36 h toafford 5 (28.4 g, 89.0 %).1HNMR (300 MHz, CDCl3): delta 3.08 (t,J = 5.1 Hz, 2H), 3.96 (t, J = 5.1Hz, 2H), 4.27 (s, 2H), 7.09-7.21 (m, 5H). |
68% | With sodium hydroxide; In ethanol; water; at 38 - 45℃; for 0.5h;pH 10 - 13;Industry scale; | In a 5L four-necked flask, water (3L), ethanol (IL) and 2-(phenylamino) ethanol (lkg , 7.300mol) were heated to 38 0C while stirring. Chloroacetyl chloride ( 2.47kg , 3eq ) and 45% sodium hydroxide solution (NaOH 1.9kg/H2O 3.1 1, beta.2eq) were then added simultaneously at temperature of 38-45 0C within 60 to 80 minutes; pH 10 to 13; and stirred at this temperature for 30 minutes. It was further cooled to 8 0C and stirred at this temperature for another 30 minutes. The precipitated product was filtered off and washed twice with 2.5kg water, each time of demineralised water at 2 0C. The moist product is dried to constant mass at 50 0C under reduced pressure to obtain 1.4kg of product (Yield 68%). |
62% | With sodium hydroxide; In isopropyl alcohol; at 0 - 40℃;pH 7 - 8; | Example 1: Preparation of 4-phenylmorpholin-3-one To a solution of 2-anilino ethanol (6.0 mL, 47.8 mmol) in IPA (6 mL) heated to 40 C were simultaneously added dropwise chloroacetyl chloride (11.4 mL, 143.4 mmol) and 10 N NaOH (29.6 mL, 296 mmol) maintaining the pH around 7-8. After the addition, the mixture was stirred at 40 C for 10 min, was cooled to 0 C and was stirred at this temperature for 1 h. The white solid formed was collected by filtration, washed with cold water and dried, affording 4- phenylmorpholin-3-one (5.27 g, 62%) as a white solid. 1H NMR (400 MHz, CDCI3) delta 7.42 (t, J = 8.0 Hz, 2 H), 7.34-7.27 (m, 3 H), 4.35 (s, 2 H). 4.04 (t, J = 5.2 Hz, 2 H), 3.77 (t, J = 5.2 Hz, 2 H). |
62.5% | With sodium hydroxide; In ethanol; water; at 0 - 41℃; for 2h;pH 12 - 12.5;Product distribution / selectivity; | A 250-mL flask was charged with 2-anilinoethanol (9.17 ml, 73.2 mmol), 9 mL dry EtOH, an overhead stirrer, a calibrated pH probe, and 27 niL water. An addition funnel was charged with 10 N sodium hydroxide solution (45.4 ml, 454 mmol). The solution was heated to 41 C, and treated with chloracetyl chloride (17.5 ml, 220 mmol) via a syringe pump over 1 h. The sodium hydroxide solution was simultaneously added to the stirring solution so that the pH was maintained between 12 and 12.5. After the addition was complete, the solution was cooled to 0 C and stirred for 1 h. The solids were collected and washed with water (2 X 60 mL cold water). The solids were dried at 50 0C at 0.2 mm Hg for 36 h to afford 4-phenylmorpholin-3-one (8.10 g, 62.5% yield). 1H NMR (400 MHz, CHLOROFORM-d) 3.75 - 3.80 (m, 2 H) 4.02 - 4.06 (m, 2 H) 4.35 (s, 2 H) 7.27 - 7.36 (m, 3 H) 7.39 - 7.46 (m, 2 H). 13C NMR (101 MHz, CHLOROFORM-d) 49.69 (s, 1 C) 64.14 (s, 1 C) 68.57 (s, 1 C) 125.48 (s, 2 C) 127.15 (s, 1 C) 129.30 (s, 2 C) 141.31 (s, 1 C) 166.59 (s, 1 C). |
With sodium hydroxide; In ethanol; water; | 1st Step: 4-phenyl-3-morpholinone (VIII) In a 26-litre tank, 1.65 kg (12.0 mol) of 2-anilinoethanol are dissolved at room temperature in 1.53 l of ethanol and subsequently admixed with 4.58 l of water with stirring. The solution is heated to 38 C. 4.07 kg (3.0 equivalents) of chloroacetyl chloride and 6.60 kg of 45% sodium hydroxide solution (6.2 equivalents) are then added simultaneously at an internal temperature of 38 to 43 C. within 60 to 80 minutes, so that the pH is kept between 12 and 12.5. The mixture is stirred at a pH of 12 to 12.5 for 10 minutes, then cooled to 2 C. and stirred at this temperature for 30 minutes. The precipitated product is filtered off and washed twice with 3.3 kg each time of demineralized water at 2 C. | |
With sodium hydroxide; In water; isopropyl alcohol; at 35 - 40℃; for 1h;pH 12.5 - 13.0; | 100 ml IPA and 100 g 2-phenylaminoethanol were added to RBF at 25C to 35C followed by stirring for 10 min. To the reaction mass 100 ml water added and temperature raised to 35C to 40C. Further NaOH solution (180.78 g NaOH + 350 mL water) was added in pressure equalizing funnel. Similarly 246.98 g chloroacetyl chloride was added in another pressure equalizing dropping funnel. The NaOH solution and chloroacetyl chloride were added simultaneously at such a rate that pH maintained between 12.5-13.0. The reaction mass was stirred for 60 min. 35C to 40C water to afford title compound as 4-Phenylmorpholin-3-one (A) | |
With sodium hydroxide; In water; isopropyl alcohol; at 25 - 40℃; for 1h;pH 12.5-13.0; | 100 ml IPA and 100 g 2-phenylaminoethanol were added to RBF at 25 C. to 35 C. followed by stirring for 10 min. To the reaction mass 100 ml water added and temperature raised to 35 C. to 40 C. Further NaOH solution (180.78 g NaOH+350 mL water) was added in pressure equalizing funnel. Similarly 246.98 g chloroacetyl chloride was added in another pressure equalizing dropping funnel. The NaOH solution and chloroacetyl chloride were added simultaneously at such a rate that pH maintained between 12.5-13.0. The reaction mass was stirred for 60 min. 35 C. to 40 C. water to afford title compound as 4-Phenylmorpholin-3-one (A) | |
With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 60℃; for 4h; | Chloroacetyl chloride was added indrop wise manner in a previously cooled round bottom flaskcontaining INT-a (0.01 mol), DMF and K2CO3 (0.02 mol)maintain the temperature at 0 C. After completion of theaddition, raise the temperature at 60 C and maintain further 4 hprogress of the reaction was monitored on TLC (Scheme-I). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With potassium tert-butylate; In tetrahydrofuran; at 38℃; for 16h;Inert atmosphere; | 1 g of phenylaminoethanol and 0.834 g of potassium t-butoxide were placed in a three-necked flask.Then add 10 mL of anhydrous tetrahydrofuran as a solvent under the protection of nitrogen.The oil bath is fully stirred and dissolved, and the oil bath temperature is 38 C.Then add 1 mL of ethyl chloroacetate.The reaction was continued for 16 h to give 4-phenyl-3-morpholinone.After the reaction, the solvent tetrahydrofuran was first spun out using a rotary evaporator.Then add a small amount of ethyl acetate for extraction and separation.The organic phases were combined, dried over anhydrous sodium sulfate and distilled under reduced pressure.After separation by column chromatography,Recrystallization from petroleum ether gave 4-phenyl-3-morpholinone.The yield was 83%. |
Tags: Rivaroxaban Impurity 54 | 122-98-5
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P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
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P233 | Keep container tightly closed. |
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P240 | Ground/bond container and receiving equipment. |
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P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
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P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
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P285 | In case of inadequate ventilation wear respiratory protection. |
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Code | Phrase |
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P304 | IF INHALED: |
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P378 | |
P380 | Evacuate area. |
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P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
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P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
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P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
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H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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