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Chemical Structure| 4542-47-6 Chemical Structure| 4542-47-6

Structure of 3-(4-Morpholino)propionitrile
CAS No.: 4542-47-6

Chemical Structure| 4542-47-6

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Product Details of [ 4542-47-6 ]

CAS No. :4542-47-6
Formula : C7H12N2O
M.W : 140.18
SMILES Code : N#CCCN1CCOCC1
MDL No. :MFCD00006178
InChI Key :WXVKGHVDWWXBJX-UHFFFAOYSA-N
Pubchem ID :78298

Safety of [ 4542-47-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H227-H302+H312+H332-H315-H319
Precautionary Statements:P210-P261-P264-P270-P271-P280-P301+P312+P330-P302+P352+P312+P362+P364-P304+P340+P312-P305+P351+P338+P337+P313-P370+P378-P403+P235-P501

Application In Synthesis of [ 4542-47-6 ]

* 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.

  • Downstream synthetic route of [ 4542-47-6 ]

[ 4542-47-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 4542-47-6 ]
  • [ 60186-33-6 ]
  • C23H26N2O3 [ No CAS ]
  • 2
  • [ 4542-47-6 ]
  • [ 32024-15-0 ]
  • 3-morpholino-2-(5-iodo-3,4-dimethoxybenzyl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
The general method of Roth et al. [29] was modified. A solution of 6.92 g (54.1 mmol) of 9 in 20 mL of anhydrous DMSO was treated with 0.29 g (5.40 mmol) of sodium methoxide, and heated at 70-72 C. A warm solution of 12.2 g (41.8 mmol) of 11 in 15 mL of DMSO was added to the solution of 9 over 15 min, and stirring was continued at 72 C for 45 min. The crude reaction mixture was cooled in an ice bath, and 40 mL of ice-cold water was added. The mixture was extracted with dichloromethane (3 × 100 mL), and the combined organic layers were washed with saturated NaCl, dried (MgSO4), and concentrated under vacuum to give 3-morpholino-2-(5-iodo-3,4-dimethoxybenzyl)acrylonitrile (12) as dark red oil. This crude material was dissolved in dry ethanol, 6.76 g (52.2 mmol) of aniline hydrochloride was added, and the mixture was refluxed for 1 h. While the mixture was still hot, 9.55 g (100 mmol) of guanidine hydrochloride was added, followed by 9.00 g (167 mmol) of sodium methoxide (Caution. The initial addition must be done very slowly). The reaction mixture was then heated under reflux for 3 h and concentrated under vacuum to one-third volume. The mixture was cooled to 0 C for 30 min, and 40 mL of ice-cold water was added. The resulting crude product was filtered, washed with water and recrystallized twice (4:1 ethanol:water) to give 13 (9.68 g, 60%) as a tan solid, mp 217-218 C. IR: 3467, 3315, 3140, 1638 cm-1; 1H NMR (DMSO-d6, 300 MHz): δ 7.57 (s, 1H), 7.14 (d, 1H, J = 1.8 Hz), 6.98 (d, 1H, J = 1.8 Hz), 6.16 (br s, 2H), 5.77 (br s, 2H), 3.77 (s, 3H), 3.66 (s, 3H), 3.54 (s, 2H); 13C NMR (DMSO-d6, 75 MHz): δ 162.4, 162.1, 156.0, 152.0, 146.3, 138.9, 129.1, 113.8, 105.2, 92.4, 59.8, 55.8, 31.7.
General procedure: The condensation reactions of halogenated dimethoxy benzaldehydeadducts (2a, 2b, or 2c) and 3-morpholinopropio nitrile (3) wereconducted based on the previously reported procedure.15 Compound 3(11.49 mmol), prepared based on previously reported procedure.20 wasdissolved in DMSO (3.0 mL) and heated to 65 C. Into a preheated solution,a freshly prepared sodium methoxide (4.59 mmol) was slowlyadded and stirred for 45 min at 80 C. Then, a solution of 2 (9.19 mmol)in DMSO (5.0 mL) was added into the heated solution. The reaction wasstirred at 80 C for 16 h. The reaction was quenched with diluted HCl(1:2 of 1M HCl in H2O) and extracted with CH2Cl2. An organic layerwas subsequently washed with water and saturated NaCl solution. Thewashed organic layer was dried over Na2SO4. The solvent was removedunder reduced pressure, affording dark brown viscous liquid. The crudeproduct was partially purified by column chromatography to give ayellow to brown viscous liquid mixture. The mixture was carried on tothe next step.
With sodium methylate; In dimethyl sulfoxide; at 70 - 72℃; for 1h;Inert atmosphere; The general method of Roth etal. [38] was modified. To a stirred solution of 1 (6.92g, 54.1mmol) in DMSO (20mL), NaOMe (0.29g, 5.40mmol) was added and heated at 70-72C. A pre-heated solution of 2 (12.2g, 41.8mmol) in DMSO (15mL) was added to the reaction mixture dropwise over a period of 15min and the reaction was heated for an additional 45min. The crude reaction mixture was poured into cold ice water (50mL) and extracted with DCM (3×100mL). The combined organic layers were washed with satd. NaCl (100mL), dried (MgSO4) and concentrated under vacuum to give 3-morpholino-2-(5-iodo-3,4-dimethoxybenzyl)acrylonitrile (90%) as a dark red oil. The crude material was further dissolved in ethanol (75mL), followed by addition of aniline hydrochloride (6.76g, 52.2mmol), and refluxed for 1h. During the reflux, guanidine hydrochloride (9.55g, 100mmol) and sodium methoxide (9.00g, 167mmol) were added and the reflux was continued for an additional 3h. The reaction mixture was then concentrated to 1/3rd volume and cooled to 0C for 30min. Addition of ice-cold water (40mL) and stirring resulted in an off-white product as a precipitate. The resulting crude product was filtered, washed and recrystallized (EtOH:H2O (4:1)) to give 3 (9.68g, 60%) as a tan solid, mp 217-218C. IR: 3467, 3315, 3140, 1638cm-1; 1H NMR (DMSO-d6, 300MHz): δ 7.57 (s, 1H), 7.14 (d, 1H, J=1.8Hz), 6.98 (d, 1H, J=1.8Hz), 6.16 (br s, 2H), 5.77 (br s, 2H), 3.77 (s, 3H), 3.66 (s, 3H), 3.54 (s, 2H); 13C NMR (DMSO-d6, 75MHz): δ 162.4, 162.1, 156.0, 152.0, 146.3, 138.9, 129.1, 113.8, 105.2, 92.4, 59.8, 55.8, 31.7.
 

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[ 4542-47-6 ]

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