Alternatived Products of [ 117977-18-1 ]
Product Details of [ 117977-18-1 ]
| CAS No. : | 117977-18-1 |
MDL No. : | MFCD06658538 |
| Formula : |
C11H17NO3
|
Boiling Point : |
- |
| Linear Structure Formula : | - |
InChI Key : | - |
| M.W : |
211.26
|
Pubchem ID : | - |
| Synonyms : |
|
Safety of [ 117977-18-1 ]
Application In Synthesis of [ 117977-18-1 ]
* 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.
- Upstream synthesis route of [ 117977-18-1 ]
- Downstream synthetic route of [ 117977-18-1 ]
- 1
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[ 59886-90-7 ]
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[ 1589-49-7 ]
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[ 117977-18-1 ]
| Yield | Reaction Conditions | Operation in experiment |
| 95% |
|
128 g (1.42 mol) 3-methoxy -1-propanol was dissolved in 250 ml of dimethyl sulfoxide to obtain a solution. 76.1 g (1.9mol) of sodium hydroxide was added to this solution at room temperature. The obtained mixture was stirred at 6O0C for 2 hrs and 15O g (0.954 mol) of 4-chloro- 2,3-lutidine-N-oxide was added. The reaction mixture was stirred at 75 0C for 5 hrs. After the completion of reaction, mixture cooled to 200C & quenched in 2 liter of water under stirring. Reaction mixture was extracted with chloroform (500 ml X 3). The organic phases were combined & dried over sodium sulfate and chloroform was concentrated under reduced pressure to obtained 195 g (95 %) of title compound as brown oil |
| 84.6% |
With sodium hydroxide;N-methyl-tri-n-butyl-ammonium bromide; In water; at 100℃; for 8h; |
397.8 g (4.41 mol) of 3-<strong>[1589-49-7]methoxypropanol</strong> were added to 95 g (0.6 mol) of 4-chloro-2,3-dimethylpyridine N-oxide and 17 g (0.06 mol) of tributylmethylammonium bromide. 101.4 ml of 50% NaOH were added dropwise to the clear solution. The reaction mixture was heated to 100 C. and stirred at this temperature for 8 h. The reaction mixture was filtered through a G3 glass frit. Subsequently, the organic phase was removed and the aqueous phase diluted with water and extracted repeatedly with dichloromethane. The filter cake was washed with dichloromethane and the organic phases were combined and washed with water. After removal of the solvent, 101.8 g (84.6%) of a brown oil remained which had a content of 96.8% of 4-(3-methoxypropoxy)-2,3-dimethylpyridine N-oxide. |
| 84.6% |
With sodium hydroxide; N-methyl-tri-n-butyl-ammonium bromide; In water; at 110℃; for 8h; |
397,8g (4,41 mol) 3-Methoxypropanol wurden zu 95g (0,6mol) 4-Chloro-2,3-dimethylpyridin-N-oxid und 17g (0,06mol) Tributylmethylammoniumbromid gegeben. Zu der klaren Loesung wurden 101,4 ml einer 50%igen NaOH tropfenweise zugegeben. Die Reaktionsmischung wurde auf 100C erhitzt und 8h bei dieser Temperatur geruehrt. Die Reaktionsmasse wurde ueber eine G3-Glasfritte filtriert. Anschliessend wurde die organische Phase abgetrennt und die waessrige Phase mit Wasser verduennt und mehrmals mit Dichlormethan extrahiert. Der Filterkuchen wurde mit Dichlormethan gewaschen und die organischen Phasen vereinigt und mit Wasser gewaschen. Nach dem Entfernen des Loesungsmittels verblieben 101,8g (84,6%) eines braunen Oels, das einen Gehalt von 96,8% an 4-(3-Methoxypropoxy)-2,3-dimethylpyridin-N-oxid aufweist. |
|
In dimethyl sulfoxide; |
PREPARATIVE EXAMPLE 13 4-(3-Methoxypropoxy)-2,3-dimethylpyridine N-oxide STR91 2.0 g (22 mmol) of 3-<strong>[1589-49-7]methoxypropanol</strong> was dissolved in 50 ml of dimethyl sulfoxide to obtain a solution. 2.7 g (66 mmol) of sodium hydride was added to this solution at a room temperature. The obtained mixture was stirred at 60 C. for one hour and cooled to a room temperature by allowing to stand, followed by the addition of 3.0 g (19 mmol) of 4-chloro-2,3-dimethylpyridine N-oxide. The obtained mixture was stirred at 40 C. for one hour. After the completion of the reaction, the reaction mixture was distilled to remove the dimethyl sulfoxide. The obtained residue was purified by silica gel column chromatography to obtain 760 mg of 4-(3-methoxypropoxy)-2,3-dimethylpyridine N-oxide. 1 H-NMR(CDCl3) delta; 2.1(m, 2H), 2.2(s, 3H), 2.54(s, 3H), 3.35(s, 3H), 3.55(t, J=6 Hz, 2H), 4.1(t, J=6 Hz, 2H), 6.65(d, J=7.4 Hz, 1H), 8.16(d, J=7.4 Hz, 1H). |
|
With sodium; In tetrahydrofuran; at 100℃; for 12h;Heating / reflux; |
7.8g sodium was suspended in 90ml 3-methoxy-1- propanol, and then the suspension was heated up to 100 C by oil bath until it turned clear completely. After cooled, 120ml THF and 30g 2,3-dimethyl-4-chloro-pyridine N-oxide were added and then the reflux reaction took place for 12 hours and was cooled again. 200ml water was added and pH value was adjusted to 7. The reaction solution was extracted with chloroform, dried with anhydrous magnesium sulfate and filtered. The filtrate was concentrated under vacuum to recover chloroform and 3-methoxy-1-propanol, the obtained product was used in the next step. |
Reference：
[1]Patent: WO2009/116072,2009,A2 .Location in patent: Page/Page column 12
[2]Organic Process Research and Development,2010,vol. 14,p. 562 - 567
[3]Patent: US2004/63957,2004,A1 .Location in patent: Page 4
[4]Patent: EP1405847,2004,A1 .Location in patent: Page 6
[5]Patent: US5045552,1991,A
[6]Patent: EP1795195,2007,A1 .Location in patent: Page/Page column 5
[7]Asian Journal of Chemistry,2013,vol. 25,p. 7959 - 7966
- 2
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[ 117977-18-1 ]
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[ 117977-19-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|
With acetic anhydride; sodium hydrogencarbonate |
P.14 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine STR92
PREPARATIVE EXAMPLE 14 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine STR92 20 ml of acetic anhydride was added to 760 mg (3.6 mmol) of 4-(3-methoxypropoxy)-2,3-dimethylpyridine N-oxide to carry out the reaction at 90° C. for one hour. The reaction mixture was distilled to remove the acetic anhydride, followed by the addition of a saturated aqueous solution of sodium hydrogencarbonate. The obtained mixture was extracted with chloroform. The extract was concentrated to obtain 700 mg of 2-acetoxymethyl-4-(3-methoxypropoxy)-3-methylpyridine as a brown oil. |
- 3
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[ 117977-18-1 ]
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[ 108-24-7 ]
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[ 117977-19-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|
With sulfuric acid In water at 90℃; for 3h; |
2
50g 4-(3-methoxy-propoxy)-2,3-dimethyl-pyridine N-oxide, 150ml acetic anhydride and 8 drops of concentrated sulfuric acid were put into a reaction flask and reacted at 90 °Cfor 3 hours in oil bath. The acetic anhydride was vaporized under vacuum. 100ml water and 20g sodium hydroxide at ambient temperature were added to the flask and reacted at 50 °C for 1 hour in water bath. And then the reaction solution was cooled, extracted by chloroform, dried, filtered and concentrated till dry. 200ml fresh chloroform and 30ml thionyl chloride were added to the residue and the reaction took place at ambient temperature for 5 hours and the reaction solution was concentrated under vacuum. After that, 400ml water was added to the residue and the pH value was adjusted to 8 with sodium carbonate solution. Finally, the expected product (brown semi-solid) was produced after the procedures of extracting the reaction solution by chloroform, drying and concentration. |
|
at 0 - 90℃; |
3
145 g (1.42 mol) of the acetic anhydride was added over 30 minutes to 150 g (0.71 mol) of 4-(3-methoxy propoxy)-2, 3-dimethyl pyridine-N-oxide at O0C. The solution was heated to 900C and stirred for 6 hrs. After the completion of reaction, it was distilled under reduced pressure to remove acetic anhydride. The obtained residue containing 2- acetoxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine was added in 34.2 g (0.85 mol) of sodium hydroxide & 450 ml of ethanol at room temperature. The reaction mixture was stirred at 55 0C for 2 hrs. After completion of reaction, remove ethanol by distillation under reduced pressure. The obtained residue was diluted with 1500 ml of water & extracted with methylene dichloride (500 ml X 2 & 100 ml X 1). The combined organic layer was dried over sodium sulfate. The methylene dichloride layer was concentrated to obtain 98 g (79 %) of 2-hydroxymethyl -4-(3-methoxy propoxy)-3 -methyl pyridine as brown oil |
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With acetic acid In methanol; toluene |
|
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at 0 - 90℃; for 6.5h; Inert atmosphere; |
|
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With toluene-4-sulfonic acid at 50℃; for 3h; |
1-3 Preparation of 3-methyl-2-hydroxymethyl-4-(3-methoxypropoxy)pyridine
Mix 50g of 2,3-dimethyl-4-(3-methoxypropoxy)pyridine nitroxide, 97g of acetic anhydride,Add 4g of p-toluenesulfonic acid into the reaction flask, stir evenly and then raise the temperature, control the temperature at 50±5 and react for 3 hours after TLC,The results showed that the raw materials were completely reacted (the reaction solution was detected by HPLC, the purity of the target product was 94.9%), and the excess acetic anhydride was concentrated under negative pressure.Add 10% sodium hydroxide aqueous solution, adjust the pH to 14 and then raise the temperature to 80°C for 1 hour.After confirming the completion of the reaction by TLC, it was lowered to room temperature, extracted with toluene and concentrated to dryness to obtain the compound shown in the title with a molar yield of 92.1% and a purity of 95.52%. |
Reference：
[1]Current Patent Assignee: HANSOH PHARMACEUTICAL GROUP CO LTD - EP1795195, 2007, A1
Location in patent: Page/Page column 5
[2]Current Patent Assignee: IPCA LABORATORIES LIMITED - WO2009/116072, 2009, A2
Location in patent: Page/Page column 12-13
[3]Sharada; Satyanarayana Reddy; Sammaiah; Sumalatha
[Asian Journal of Chemistry, 2013, vol. 25, # 14, p. 7959 - 7966]
[4]Wang, Dong; Liu, Zhenlin; Wang, Zhentao; Ma, Xinyue; Yu, Peng
[Green Chemistry, 2019, vol. 21, # 1, p. 157 - 163]
[5]Current Patent Assignee: RUNDU PHARMACEUTICAL WUHAN RES INSTITUTE; ZHUHAI RUNDU PHARMACEUTICAL CO LTD - CN111704573, 2020, A
Location in patent: Paragraph 0017-0019
- 4
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[ 117977-18-1 ]
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[ 153259-31-5 ]
| Yield | Reaction Conditions | Operation in experiment |
|
Multi-step reaction with 3 steps
1: acetic acid / methanol; toluene
2: sodium hydroxide / methanol
3: thionyl chloride |
|
|
Multi-step reaction with 3 steps
1: trifluorormethanesulfonic acid / 5 h / 30 °C
2: sodium hydroxide; water / 1 h / 80 °C / pH 14
3: thionyl chloride / ethyl acetate / 3 h / 5 - 20 °C |
|
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Multi-step reaction with 3 steps
1: toluene-4-sulfonic acid / 3 h / 50 °C
2: sodium hydroxide; water / 1 h / 80 °C / pH 14
3: thionyl chloride / ethyl acetate / 3 h / 5 - 20 °C |
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- 5
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[ 117977-18-1 ]
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[ 675198-19-3 ]
- 6
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[ 117977-18-1 ]
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[ 75-36-5 ]
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[ 117977-19-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|
With trifluorormethanesulfonic acid at 15 - 35℃; for 5h; |
2
,3-dimethyl-4- (methoxypropoxy) - pyridin-oxide -N- 110g was mixed with 12g of trifluoromethanesulfonic acid was slowly added dropwise at room temperature with acetyl chloride 64g, dropwise addition , the reaction was kept between 15 ~ 35 5 hours; after the end of the incubation the reaction was slowly added to 185ml of water, with sodium hydroxide solution the system was adjusted to pH 13 to 14, and then warmed to 60 ~ 65 incubated for 5 hours; insulation after cooling to room temperature, 340ml of toluene was added, phases were separated, the aqueous phase was extracted twice with toluene and the combined toluene phases were concentrated to dryness under reduced pressure to give a concentrate of about 87g, was dissolved with 150ml of ethyl acetate, cooled to below 5 , then treated with HCl saturated ethyl acetate solution was adjusted pH = 3 ~ 4, crystallization was stirred for about 2 hours or less 5 ; filtered off with suction, the filter cake was washed with cold acetone, dried under reduced pressure at about 40 , pale yellow or almost white 2-hydroxymethyl-4- (methoxypropoxy) -3-methylpyridine hydrochloride about 84g, purity (HPLC) 98.0%. |
|
With trifluorormethanesulfonic acid at 30℃; for 5h; |
1 Preparation of 3-methyl-2-acetoxymethyl-4-(3-methoxypropoxy)pyridine (Formula III)
Mix 11g of 2,3-dimethyl-4-(3-methoxypropoxy)pyridine nitroxide with 1.2g of trifluoromethanesulfonic acid, and slowly add 6.4g of acetyl chloride dropwise at room temperature,After dripping, the reaction was kept at 30°C for 5 hours, and the reaction solution was taken for HPLC analysis. 5.1% of the 3-acetoxymethyl product and 11.3% of the compound of formula IV were not converted.The reaction time was prolonged by 3h, and the reaction liquid was taken for HPLC analysis, and the quality of the reaction liquid had no obvious change.The temperature was raised to 50°C, the reaction was carried out for 1 hour, and the reaction solution was taken for HPLC analysis. The product contained 14.8% of the 3-acetyl methoxy group. |
- 7
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[ 117977-18-1 ]
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[ 117977-21-6 ]
- 8
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[ 117977-18-1 ]
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[ 118175-10-3 ]
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