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Product Details of 4-Chloropyridine HCl

CAS No. :7379-35-3
Formula : C5H5Cl2N
M.W : 150.01
SMILES Code : ClC1=CC=NC=C1.[H]Cl
MDL No. :MFCD00012829
InChI Key :XGAFCCUNHIMIRV-UHFFFAOYSA-N
Pubchem ID :81852

Safety of 4-Chloropyridine HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 4-Chloropyridine HCl

* 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 [ 7379-35-3 ]
  • Downstream synthetic route of [ 7379-35-3 ]

[ 7379-35-3 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 7379-35-3 ]
  • [ 108-95-2 ]
  • [ 4783-86-2 ]
References: [1] Tetrahedron Letters, 2006, vol. 47, # 29, p. 5045 - 5048.
[2] Patent: US6500948, 2002, B1, .
[3] Patent: US6153757, 2000, A, .
[4] Patent: US6750228, 2004, B1, .
[5] Tetrahedron Letters, 2010, vol. 51, # 2, p. 248 - 251.
[6] Patent: US2010/174089, 2010, A1, . Location in patent: Page/Page column 4.
  • 2
  • [ 110-89-4 ]
  • [ 7379-35-3 ]
  • [ 2767-90-0 ]
References: [1] European Journal of Medicinal Chemistry, 2001, vol. 36, # 3, p. 215 - 225.
[2] Synlett, 2000, # 1, p. 116 - 118.
[3] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 21, p. 6122 - 6126.
[4] Tetrahedron Letters, 2004, vol. 45, # 4, p. 757 - 759.
[5] Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 2627 - 2645.
  • 3
  • [ 7379-35-3 ]
  • [ 100-51-6 ]
  • [ 49826-70-2 ]
YieldReaction ConditionsOperation in experiment
89%
Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 5℃; for 0.25 h;
Stage #2: at 5 - 60℃;
A flask is charged with NaH (60percent dispersion in mineral oil, 0.72 g, 18.0 mmol) then suspended in DMF (30 mL) and cooled to 5° C. To this mixture is added benzyl alcohol (1.04 mL, 10.0 mmol) drop-wise. The mixture is stirred for 15 minutes then 4-chloropyridine-HCl (1.00 g, 6.67 mmol) is added in three portions over 5 min. The resulting mixture is stirred at 5° C. for 10 min then warmed to 60° C. and stirred for 1.5 h. The mixture is then cooled to 23° C., treated with water, and extracted with EtOAc. The combined organics are dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, 5percent EtOAc in hexanes to 50percent EtOAc in hexanes) gives the title intermediate (1.10 g, 89percent).
89%
Stage #1: With sodium hydride In N,N-dimethyl-formamide; mineral oil at 5℃; for 0.25 h;
Stage #2: at 5 - 60℃; for 1.75 h;
Example 3
Synthesis of 4-(benzyloxy)pyridine.
A flask is charged with NaH (60percent dispersion in mineral oil, 0.72 g, 18.0 mmol) then suspended in DMF (30 mL) and cooled to 5 °C.
To this mixture is added benzyl alcohol (1.04 mL, 10.0 mmol) drop-wise.
The mixture is stirred for 15 minutes then 4-chloropyridine-HCl (1.00 g, 6.67 mmol) is added in three portions over 5 min.
The resulting mixture is stirred at 5 °C for 10 min then warmed to 60 °C and stirred for 1.5 h.
The mixture is then cooled to 23 °C, treated with water, and extracted with EtOAc.
The combined organics are dried with MgSO4, filtered, and concentrated in vacuo.
Purification of the crude by flash chromatography (SiO2, 5percent EtOAc in hexanes to 50percent EtOAc in hexanes) gives the title intermediate (1.10 g, 89percent).
References: [1] Journal of Organic Chemistry, 2017, vol. 82, # 24, p. 13756 - 13767.
[2] Patent: US2011/275627, 2011, A1, . Location in patent: Page/Page column 60.
[3] Patent: EP2331541, 2011, A1, . Location in patent: Paragraph 0070; 0071.
  • 4
  • [ 7379-35-3 ]
  • [ 142-84-7 ]
  • [ 69008-70-4 ]
YieldReaction ConditionsOperation in experiment
81.2% at 110℃; for 8 h; Large scale Dipropylamine 90 kg was drawn into a 200 L reaction shaft,Add 4-chloropyridine hydrochloride 30kg,Potassium fluoride 12kg, the temperature was raised to 110 , incubated for 8 hours,Decompression recovery dipropylamine, sodium bicarbonate solution while hot to adjust the pH to about 8, adding petroleum ether 150kg,Separation of the water layer, the organic layer cooling, filtration, drying too28.9 kg of 4-dipropylaminopyridine,Purity 98.1percent, yield 81.2percent.
References: [1] Patent: CN107501173, 2017, A, . Location in patent: Paragraph 0020.
[2] European Journal of Organic Chemistry, 2013, # 24, p. 5423 - 5430.
  • 5
  • [ 111-86-4 ]
  • [ 7379-35-3 ]
  • [ 64690-19-3 ]
YieldReaction ConditionsOperation in experiment
78.5% at 130℃; for 2 h; Large scale Into 200L reactor was pumped n-octylamine 100kg,30kg of 4-chloropyridine hydrochloride and 10kg of sodium fluoride were added, the temperature was raised to 130 ° C, and the mixture was stirred for 2 hours while keeping warm,Decompression recovery n-octylamine, while hot sodium carbonate aqueous solution to adjust the pH to about 7, adding ethyl acetate 120kg, separating the aqueous layer, the organic layer was cooled, filtered,Dried to give 4-octylaminopyridine 32.3kg,Purity was 99.3percent, yield was 78.5percent.
References: [1] Journal of the American Chemical Society, 2008, vol. 130, # 20, p. 6586 - 6596.
[2] Patent: CN107501173, 2017, A, . Location in patent: Paragraph 0018.
  • 6
  • [ 142-95-0 ]
  • [ 7379-35-3 ]
  • [ 64690-19-3 ]
YieldReaction ConditionsOperation in experiment
93% at 120 - 200℃; for 7 h; 5.0 g (0.0333 mol) of 4-chlororpyridine hydrochloride,And 0.55 g (0.0333 mol) of n-OCtylaminehydrochloride,The mixture is stirred and heated from 120 ° C to 180 ° C, heated to 200 ° C and held for 7 hours. The reaction was confirmed by thin-layer chromatography, and after completion, it was cooled and cooled to 100 ° C. To the reaction solution was added 20 ml of water and the mixture was cooled with stirring.To the reaction mixture was added 35percent aqueous solution of sodium hydroxide to make it alkaline. The mixture was extracted three times with 20 ml of di-dichloromethane (MC). The organic layer was collected, washed with 10 ml of cold water, washed with saturated brine, dehydrated with magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure, 14 ml of hexane was added to the residue solid, and the mixture was refluxed and cooled. The resulting crystals were filtered, dried under reduced pressure at room temperature. [0103] 6.4 g of octylaminopyridine base (yield: 93.0percent, MP 65-69 ° C) was obtained through the above-mentioned procedure.
References: [1] Patent: KR2017/13425, 2017, A, . Location in patent: Paragraph 0099; 0100.
[2] Patent: US4206215, 1980, A, .
  • 7
  • [ 7379-35-3 ]
  • [ 189449-41-0 ]
References: [1] Synlett, 2013, vol. 24, # 1, p. 49 - 52.
 

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