* 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.
With potassium <i>tert</i>-butylate In tetrahydrofuran at 38℃; for 16 h; 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 83percent.
With sodium hydroxide In ethanol; water at 0 - 38℃; for 2 h;
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 percent).1HNMR (300 MHz, CDCl3): δ 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 0.5 h; 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 45percent sodium hydroxide solution (NaOH 1.9kg/H2O 3.1 1, β.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 68percent).
62%
With sodium hydroxide In isopropyl alcohol at 0 - 40℃;
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, 62percent) as a white solid. 1H NMR (400 MHz, CDCI3) δ 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 2 h;
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, 62.5percent 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).
Reference：
[1] European Journal of Medicinal Chemistry, 2015, vol. 95, p. 388 - 399
[2] Patent: WO2005/26135, 2005, A1, . Location in patent: Page/Page column 6
[3] Patent: WO2011/12321, 2011, A1, . Location in patent: Page/Page column 30
[4] Helvetica Chimica Acta, 2013, vol. 96, # 11, p. 2160 - 2172
[5] Patent: WO2011/80341, 2011, A1, . Location in patent: Page/Page column 14; 15
[6] Patent: WO2006/116713, 2006, A1, . Location in patent: Page/Page column 209-210; 213-214
[7] Patent: US2007/66611, 2007, A1,
[8] Journal of Chemical Research, 2011, vol. 35, # 7, p. 400 - 401
[9] Patent: WO2013/98833, 2013, A2, . Location in patent: Page/Page column 35-36
[10] Patent: US2014/378682, 2014, A1, . Location in patent: Paragraph 0186; 0187
3
[ 92-53-5 ]
[ 29518-11-4 ]
[ 13238-43-2 ]
Yield
Reaction Conditions
Operation in experiment
46%
With ozone In acetonitrile at 25℃; for 24 h;
Ozone was bubbled for 15 min in 1 L of the appropriate solvent at the selected temperature. The content of ozone was measured by iodometric titration.35N-Phenylmorpholine 1 in the amount for the appropriate stoichiometry with ozone was then added to the solution. After 24 h reaction, the suspension was filtered, evaporated at reduced pressure, and the residue was separated by flash chromatography over silica gel (R=100) eluting with the mixture dichloromethane/ethyl acetate 9:1.4.3.1. N-Phenylmorpholinone (2)White powder: IR (CaF2): 1655 cm-1; MS: m/z=177 (M+), 148 (M+-CHO), 119 (M+-2CHO), 101 (M+-2CHO-CH3); 1H NMR (400 MHz, CDCl3): δ 3.07 (t, J=5.1 Hz, 2H), 3.97 (t, J=5.1 Hz, 2H), 4.28 (s, 2H), 7.10-7.20 (m, 5H); 13C NMR (100 MHz, CDCl3): δ 161.0, 129.0, 126.5, 124.0, 60.0, 43.5, 28.5.4.3.2. Compound 3Yellow oil: IR (CaF2): 1725, 1675 cm-1; MS: m/z=193 (M+), 165 (M+-CO), 147 (M+-HCOOH), 134 (M+-CO-CHO); 1H NMR (400 MHz, CDCl3): δ 4.03 (t, J=5.1 Hz, 2H), 4.27 (t, J=5.1 Hz, 2H), 7.05-7.40 (m, 5H), 7.91 (s, 1H), 8.34 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 161.0, 160.0, 141.0, 130.0, 126.5, 124.7, 60.3, 44.1.
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).
With nitric acid; acetic anhydride; at 0 - 25℃; for 5h;
A mixture of 177 g (1 mol) of <strong>[29518-11-4]4-phenyl-3-morpholinone</strong>,Acetic anhydride 1200ml added to the reactor,After cooling to a temperature of 0 C, 145 g (1.5 mol) of nitric acid was added dropwise and reacted at room temperature for 5 h. After recovering part of the solvent, the mixture was stirred with 3000 ml of water, filtered, washed with water and the methyl ethyl ketone was recrystallized and dried to give 190 g of pale yellow solid, 85%.
83%
With sulfuric acid; nitric acid; at -10℃; for 1h;
Example 2: Preparation of 4-(4-nitrophenyl)morpholin-3-one (compound XI). To a solution of <strong>[29518-11-4]4-phenylmorpholin-3-one</strong> (19.9 g, 0.1 1 mol) in 95% H2S04 (46.6 ml_,) cooled to -10 C was carefully added dropwise during 45 min 65% HNO3 (8 ml_(). The reddish solution obtained was stirred at this temperature for 1 h and H20 (110 mL) was added. The mixture was neutralized with 35% NH4OH until pH=7. The resulting precipitate was filtered, washed with cold water and dried, affording 4-(4-nitrophenyl)morpholin-3-one (or compound XI) (20 g, 83%) as a brown solid.1H NMR (200 MHz, CDCI3) delta 8.27 (d, J = 9.4 Hz, 2 H), 7.62 (d, J = 9.4 Hz, 2 H), 4.38 (s, 2 H), 4.08 (t, J = 5.0 Hz, 2 H), 3.85 (t, J = 5.0 Hz, 2 H).
83%
With sulfuric acid; nitric acid; at -10℃; for 1h;
To a solution of<strong>[29518-11-4]4-phenylmorpholin-3-one</strong> (19.9 g, 112.3 mol) in 98% H2SO4(46.6 ml) cooled to -10 C was carefully added dropwise during 45 min 65% HNO3(8 ml). The reddish solution obtained was stirred at this temperature for 1 hand H2O (110mL) was added. The mixture was neutralizedwith 35% NH4OH until pH=7. The resulting precipitate was filtered,washed with cold water and dried, affording the desired product (20 g, 83%yield) as a brown solid. 1H NMR (300 MHz, CDCI3) delta: 8.27(d, J = 9.4 Hz, 2 H), 7.62 (d, J = 9.4 Hz, 2 H), 4.38 (s, 2 H), 4.08(t, J = 5.0 Hz, 2 H), 3.85 (t, J = 5.0 Hz, 2 H).
81%
With sulfuric acid; nitric acid; for 2h;Cooling with ice;
0.177 g of <strong>[29518-11-4]4-phenyl-3-morpholinone</strong> was added to the round bottom flask.Add 98% concentrated sulfuric acid 2.8mL 50mmol,Stir and dissolve, then slowly add 65% concentrated nitric acid 0.1mL 14mol in an ice bath, continue to stir the reaction for 2h,4-(4-Aminophenyl)-3-morpholinone was obtained. After the reaction,Add 15 mL of water to the reaction vessel.And add a small amount of ammonia water to adjust the pH to neutral.Produce a large amount of precipitate, wash it by suction,After drying, it was recrystallized from acetone to give 4-(4-aminophenyl)-3-morpholinone.The yield is 81%
69%
With sulfuric acid; nitric acid; In sulfolane; at -5 - 30℃; for 2h;
In a three-necked flask a compound obtain according to a.) (500 g, 2.824 mol ) was introduced at temperature 10 0C in4 portions into of concentrated sulphuric acid (IL) within 30minutes . The mixture was then heated to 30 0C for 30 min- utes. The solution is cooled to -5 0C and admixed within one hour with 65% nitric acid ( 205ml ,0.98 eq ) . The mixture was stirred at -5 0C for one hour. Then the mixture was put into ice-water (2.5kg), the precipitate was filtered and washed by water (0.5L*2). 1300 mL of water are metered into the filter at 10 0C, with 25% aqueous ammonia solution (20OmL) . The suspension is admixed with 7L of acetone and heated to 50 0C. Furtheron, the phases were be separated; 12L of acetone/water mixture were distilled of which the product precipitates out. The suspension was cooled to 10 0C and stirred for a further 30 minutes, and the product was isolated. The moist product wass washed with 40OmL of cold acetone and dried at 50 0C un- der reduced pressure to obtain a 432 g of the product (Yield 69 %)
With sulfuric acid; nitric acid; at 0 - 5℃; for 2.5h;
150 ml Cone. Sulfuric acid and 100 gm 4-phenyl morpholine-3-one of Formula (A) were added to RBF at 25C to 35C followed by cooling to 0C to 5C and stirring for 15 min. Further, 56.92 gm Nitric Acid (strength 70%) was added over a period of 90 min. and stirred for 60 min. at 0C to 5C. To another RBF 1.5 L process water was added at 25C to 35C and cooled to 0C to 5C. The reaction mass was added to RBF containing water at 0C to 5C and stirred for 60 min. The product was filtered and washed with 2 x 100 ml water to afford the title compound as 4-(4- Nitrophenyl)morpholin-3-one (B).
150 ml Conc. Sulfuric acid and 100 gm 4-phenyl morpholine-3-one of Formula (A) were added to RBF at 25 C. to 35 C. followed by cooling to 0 C. to 5 C. and stirring for 15 min. Further, 56.92 gm Nitric Acid (strength 70%) was added over a period of 90 min. and stirred for 60 min. at 0 C. to 5 C. To another RBF 1.5 L process water was added at 25 C. to 35 C. and cooled to 0 C. to 5 C. The reaction mass was added to RBF containing water at 0 C. to 5 C. and stirred for 60 min. The product was filtered and washed with 2*100 ml water to afford the title compound as 4-(4-Nitrophenyl)morpholin-3-one (B).
With sulfuric acid; nitric acid; at 60℃; for 3h;
In a 250 mL round bottom flask, H2SO4 (0.03 mol) was taken and cooled to 0 C. To this HNO 3(0.03 mol) was added in a drop-wise manner [12]. To thisnitrating mixture INT-b (0.01 mole) was added portion wise.After completion of the addition, reaction mixture was stirredat 60 C for 3 h reaction mixture was cooled and quince in icewater, after the confirm on TLC that reaction was completed(Scheme-I).
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%.
With ozone; In acetonitrile; at 25℃; for 24h;Mechanism;
Ozone was bubbled for 15 min in 1 L of the appropriate solvent at the selected temperature. The content of ozone was measured by iodometric titration.35N-Phenylmorpholine 1 in the amount for the appropriate stoichiometry with ozone was then added to the solution. After 24 h reaction, the suspension was filtered, evaporated at reduced pressure, and the residue was separated by flash chromatography over silica gel (R=100) eluting with the mixture dichloromethane/ethyl acetate 9:1.4.3.1. N-Phenylmorpholinone (2)White powder: IR (CaF2): 1655 cm-1; MS: m/z=177 (M+), 148 (M+-CHO), 119 (M+-2CHO), 101 (M+-2CHO-CH3); 1H NMR (400 MHz, CDCl3): delta 3.07 (t, J=5.1 Hz, 2H), 3.97 (t, J=5.1 Hz, 2H), 4.28 (s, 2H), 7.10-7.20 (m, 5H); 13C NMR (100 MHz, CDCl3): delta 161.0, 129.0, 126.5, 124.0, 60.0, 43.5, 28.5.4.3.2. Compound 3Yellow oil: IR (CaF2): 1725, 1675 cm-1; MS: m/z=193 (M+), 165 (M+-CO), 147 (M+-HCOOH), 134 (M+-CO-CHO); 1H NMR (400 MHz, CDCl3): delta 4.03 (t, J=5.1 Hz, 2H), 4.27 (t, J=5.1 Hz, 2H), 7.05-7.40 (m, 5H), 7.91 (s, 1H), 8.34 (s, 1H); 13C NMR (100 MHz, CDCl3): delta 161.0, 160.0, 141.0, 130.0, 126.5, 124.7, 60.3, 44.1.
2-(2-((methylsulfonyl)oxy)ethoxy)-N-phenylacetamide[ No CAS ]
[ 29518-11-4 ]
Yield
Reaction Conditions
Operation in experiment
85%
With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 8h;
A mixture of 2- (2 - ((methylsulfonyl) oxy) ethoxy) -n-phenyl-acetamide (136.5 g, 0.5 mol), DMF 800 ml,Potassium carbonate 138g (lmol) was added to the reaction kettle, heated at 100 C for 8 h, cooled, water added 4000ml, filtered, washed with water and dried to obtain a yellowish white solid75 g, yield 85%.
With potassium carbonate; In acetonitrile; for 6h;Reflux;
2-(2-chloroethoxy)-N-phenylacetamide 92 g (0.355 mol), acetonitrile 300ml, potassium carbonate 74g (0.536mol) was added to the reaction flask, was heated at reflux for 6h, the reaction was completed, the recovery section The solvent, water filtration, and dried to give a light yellow solid 76.6 g, 97% yield.
2-(2-((benzenesulfonyl)oxy)ethoxy)-N-phenylacetamide[ No CAS ]
[ 29518-11-4 ]
Yield
Reaction Conditions
Operation in experiment
81%
With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 8h;
A solution of 2- (2 - ((benzenesulfonyl) oxy) ethoxy) -n-phenyl-acetamide167.5 g (0.5 mol), DMF 800 ml, 138 g (1 mol) of potassium carbonate were added to the reaction vessel,Heating 100 C reaction 8h, cooling, add water, 4000ml, filtered, washed with water, dried yellowish white solid 71g, yield 81%.
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).
With caesium carbonate; at 120℃; for 14h;Schlenk technique; Inert atmosphere;
General procedure: The aryl iodide (1.5 mmol), amide (1 mmol), Cesium carbonate(1.5 mmol, 489 mg), and Cu/C (50 mg) were weighted into a Schlenk flask (10 mL) with a small magnetic stir bar. The reaction flask was evacuated and backfilled with nitrogen three times, and butyrylonitrile (3 ml) was added by syringe under nitrogen atmosphere. The resulting mixture was sealed under nitrogen and heated at 120 C for 14 h. The reaction mixture was cooled to room temperature, filtered, and the solvent removed by reduced pressure distillation. The residue was purified by silica gel flash chromatography to get the product.
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