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Chemical Structure| 135065-70-2 Chemical Structure| 135065-70-2

Structure of 135065-70-2

Chemical Structure| 135065-70-2

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Product Details of [ 135065-70-2 ]

CAS No. :135065-70-2
Formula : C12H17NO2
M.W : 207.27
SMILES Code : [C@@H]1(CNCCO1)COCC2=CC=CC=C2
MDL No. :MFCD24395785
InChI Key :LMONFJPVVMPUTF-GFCCVEGCSA-N
Pubchem ID :13670020

Safety of [ 135065-70-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362

Application In Synthesis of [ 135065-70-2 ]

* 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 [ 135065-70-2 ]

[ 135065-70-2 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 926-39-6 ]
  • [ 14618-80-5 ]
  • [ 135065-70-2 ]
YieldReaction ConditionsOperation in experiment
49% With sodium hydroxide; In methanol; water; at 50℃; Example 1; (R)-Quinuclidin-3-yl 5-((S)-2-((4-amino-5-chloro-2-ethoxybenzamido)methyl)morpholino)pentanoate [Show Image] Mono-(2-amino-ethyl) sulfate (35.2 g, 250 mmol) was dissolved in 160 mL of aqueous sodium hydroxide solution (40percent) with stirring, and to the mixture was added with a solution of (R)benzyl glycidyl ether 1a (8.2 g, 50 mmol) in methanol. The reaction mixture was reacted overnight at 50°C and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was diluted with 100 mL of water and 100 mL of concentrated hydrochloric acid, and extracted with dichloromethane (200 mL.x.3). The combined organic phase was washed successively with water (200 mL) and saturated brine (200 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (R)-2-benzyloxymethyl-morpholine 1b (5.08 g, yield 49percent) as a yellow liquid. MS m/z (ESI): 208.7 [M+1]. 1H NMR (CDCl3, 400 MHz) delta 7.4-7.2 (m, 5H), 4.56 (s, 2H), 3.9 (d, 1H, J=11Hz) 3.8-3.35 (m, 4H), 2.92 (dd, 1H, J1=2.5Hz, J2=12.0Hz), 2.85-2.75 (m, 2H), 2.66 (dd, 1H, J1=10.5Hz, J2=12.0Hz), 2.4 (s, 1H).
49% With sodium hydroxide; In methanol; water; at 50℃; Mono-(2-amino-ethyl) sulfate (35.2 g, 250 mmol) was dissolved in 160 mL of aqueous sodium hydroxide solution (40percent) with stirring, and to the mixture was added with a solution of (R)benzyl glycidyl ether 1a (8.2 g, 50 mmol) in methanol. The reaction mixture was reacted overnight at 50° C. and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was diluted with 100 mL of water and 100 mL of concentrated hydrochloric acid, and extracted with dichloromethane (200 mL.x.3). The combined organic phase was washed successively with water (200 mL) and saturated brine (200 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (R)-2-benzyloxymethyl-morpholine 1b (5.08 g, yield 49percent) as a yellow liquid.MS m/z (ESI): 208.7 [M+1].1H NMR (CDCl3, 400 MHz) delta 7.4-7.2 (m, 5H), 4.56 (s, 2H), 3.9 (d, 1H, J=11 Hz), 3.8-3.35 (m, 4H), 2.92 (dd, 1H, J1=2.5 Hz, J2=12.0 Hz), 2.85-2.75 (m, 2H), 2.66 (dd, 1H, 1H, J1=10.5 Hz, J2=12.0 Hz), 2.4 (s, 1H).
With sodium hydroxide; In water; at 55℃; Step 1: (R)-2-(Benzyloxymethyl)morpholine: A stirred mixture of (R)-benzyl glycidyl ether (16.4 g) and 2-aminoethyl hydrogen sulfate (56.4 g) was treated with a solution of sodium hydroxide (16 g) in water (33 mL). The reaction mixture was warmed to 55 0C overnight. Water (250 mL) was added and the mixture extracted into toluene (200 mL x 3). The organic layers were combined, washed with brine and then dried over magnesium sulfate, filtered and concentrated to yield the subtitle compound as a pale oil (16.5 g) which was used directly in the next step.1H NMR delta(CDCl3):1.85-2.00 (IH, br s), 2.14-2.28 (IH, m), 2.38-2.50 (IH, m), 2.60- 2.95 (3H, m), 3.39-3.55 (2H, m), 3.57-3.70 (IH, m), 3.89 (IH, dm), 4.51-4.54 (2H, ABq), 7.18-7.36 (5H, m).
With water; sodium hydroxide; In methanol; at 40℃; for 2h; Step 1. (i?)-2-(Benzyloxymethyl)morpholine: To a stirred mixture of (R)-2- (benzyloxymethyl)oxirane (10.0 g, 60.9 mmol) and NaOH (19.49 g, 487.2 mmol) in H2O (46 mL) and MeOH (18 niL), there was added 2-aminoethyl hydrogen sulfate (36.8 g, 255.8 mmol) in portions. After addition was complete, the reaction mixture was stirred at 4O0C for 2 h. After cooling, the mixture was treated with NaOH (15.0 g, 375.0 mmol), followed by toluene (70 mL), and stirred at 650C overnight. The mixture was cooled, diluted with toluene (27 mL) and H2O (92 mL). The toluene layer was separated and the aqueous layer was extracted with CH2Cl2 (2 x 50 mL). The combined organic layers were concentrated to give crude (R)-2- (benzyloxymethyl)morpholine (~14 g), which was used without purification. MS m/z 208 (M+H+).
With sodium hydroxide; In methanol; water; toluene; at 40 - 65℃; To a stirred mixture of (2R)-2-[(benzy[oxy)methy[]oxirane (27.7 g, 0.17 mo[) and NaOH (54.0 g, 1.3 mo[) in water (130 mL) and MeOH (50 mL) was added 2-aminoethy[ hydrogen su[fate (100 g, 0.7 mo[) portionwise. After addition was comp[ete, the reaction mixture was stirred at 40 °C for 2 h. On coo[ing, the mixture was treated with a further portion of NaOH (40.5 g, 1 .0 mo[), fo[[owed by to[uene (200 mL) and stirred at 65 °C overnight. The mixture was coo[ed, di[uted with to[uene and water. The to[uene [ayer was separated and the aqueous [ayerextracted with DCM (2 x 100 mL). The combined organic [ayers were concentrated to give the tit[e compound, which was used in the next step without purification.
Benzyl-(R)-glycidyl ether (2.00 g, 12.2 mmol) and NaOH (4.00 g,100 mmol) in H2O (9.2 mL) and MeOH (3.6 mL) were treated with2-aminoethyl hydrogen sulphate (7.00 g, 49.59 mmol). The reactionmixturewas stirred for 90 min at 40 °C. The mixturewas allowed tocool to room temperature, toluene (14 mL) and NaOH (2.00 g,50.0 mmol) were added and then it was stirred overnight at 65 °C.Toluene (5 mL) and H2O (20 mL) were added and the organic layerwas separated. The water layer was extracted with CH2Cl2(2 10 mL). The combined organic layers were dried over Na2SO4,filtered and concentrated in vacuo to give crude amine which wastaken up in acetone (20 mL) and H2O (6 mL) at 0 °C. Di-tert-butyldicarbonate (2.60 g, 11.9 mmol) was added and the resultingmixture was stirred vigorously for 2 h. The acetone was removedunder reduced pressure and the aqueous solution was extractedwith CH2Cl2. The organic layer was washed with brine, dried overNa2SO4, filtered and concentrated in vacuo. FCC (hexane/EtOAc10:0 ? 7:3) afforded the title compound as a colorless oil in 43percent(over 2 steps). 1H NMR (300 MHz, 80 °C, DMSO-d6) delta ppm 1.41 (s,9 H) 2.69 (dd, J 12.9, 9.4 Hz, 1 H) 2.87 (ddd, J 13.2, 11.4, 3.5 Hz,1 H) 3.28e3.56 (m, 4 H) 3.68 (ddt, J 13.2, 3.0, 1.6 Hz, 1 H)3.75e3.86 (m, 2 H) 4.50 (s, 2 H) 7.22e7.38 (m, 5 H). 13C NMR(75 MHz, 80 °C, DMSO-d6) delta ppm 27.7, 43.0, 45.3, 65.1, 70.2, 72.2,73.6, 78.7, 126.9, 127.0, 127.7, 138.0, 153.6. HRMS (ESI-TOF) m/z:[M+H]+ Calcd for C17H26NO4 308.18563; Found 308.1867.
Step 1. (R)-2-(Benzyloxymethyl)morpholine. To a stirred mixture of (R)-2-(benzyloxymethyl)oxirane (10.0 g, 60.9 mmol) and NaOH (19.49 g, 487.2 mmol) in H2O (46 mL) and MeOH (18 mL), there was added 2-aininoethyl hydrogen sulfate (36.8 g, 255.8 mmol) in portions. After addition, the reaction mixture was- stirred at 4O0C for 2 h. After cooling, the mixture was treated with NaOH (15.0 g, 375.0 mmol) then toluene (70 mL) and stirred at 650C overnight. The mixture was cooled,. diluted with toluene (27 mL) and H2O (92 mL). The toluene layer was separated and the aqueous layer was extracted with CH2CI2 (2 x 50 mL). The combined organic layers were concentrated to give crude (R)-2-(benzyloxymethyl)morpholine (~14 g), which was used without purification. MS m/z 208 (M+H+).

 

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