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Chemical Structure| 6959-47-3 Chemical Structure| 6959-47-3
Chemical Structure| 6959-47-3

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Synonyms: Picolyl chloride hydrochloride; 2-(Chloromethyl)pyridine hydrochloride

4.5 *For Research Use Only !

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Product Details of 2-(Chloromethyl)pyridine HCl

CAS No. :6959-47-3
Formula : C6H7Cl2N
M.W : 164.03
SMILES Code : ClCC1=NC=CC=C1.[H]Cl
Synonyms :
Picolyl chloride hydrochloride; 2-(Chloromethyl)pyridine hydrochloride
MDL No. :MFCD00012811
InChI Key :JPMRGPPMXHGKRO-UHFFFAOYSA-N
Pubchem ID :23392

Safety of 2-(Chloromethyl)pyridine HCl

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P261-P280-P305+P351+P338-P310
Class:8
UN#:3261
Packing Group:

Application In Synthesis of 2-(Chloromethyl)pyridine 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 [ 6959-47-3 ]
  • Downstream synthetic route of [ 6959-47-3 ]

[ 6959-47-3 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 619-08-9 ]
  • [ 6959-47-3 ]
  • [ 179687-79-7 ]
YieldReaction ConditionsOperation in experiment
98%
Stage #1: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5 h;
Stage #2: With potassium iodide In N,N-dimethyl-formamide at 60℃; for 12 h;
2-(Chloromethyl)pyridine hydrochloride (16.4 g, 0.1 mol) and K2CO3 (27.6 g, 0.2 mol) were suspended in DMF (100 mL) and stirred at room temperature for 30 min. 2-Chloro-4-nitrophenol (17.4 g, 0.1 mol) and KI (0.83 g, 5 mol percent) were added in and the reaction mixture was stirred at 60 °C for 12 h. The reaction suspension was diluted with water (400 mL) and the resulting solid was filtered, washed with water and dried to give 2-((2-chloro-4-nitrophenoxy)methyl)pyridine (26 g, 98percent) as a white solid. Mp 149.2–149.9 °C; MS-EI (m/z): 92, 229, 263(M+).
74% With potassium carbonate; sodium iodide In acetonitrileReflux Step 1:
2-((2-chloro-4-nitrophenoxy)methyl)pyridine
2-chloro-4-nitrophenol (3.4 g, 20 mmol), 2-(chloromethyl)pyridine hydrochloride (3.4 g, 21 mmol), potassium carbonate (3.3 g, 24 mmol) and sodium iodide (3.0 g, 20 mmol) were refluxed in acetonitrile (30 mL) overnight.
The reaction mixture was poured into 100 mL of H2O, extracted with ethyl acetate.
The organic phase was washed with saturated brine, dried, evaporated with rotary evaporator, to obtain the crude product.
The crude product was washed with petroleum ether, filtered and dried, and the compound shown in the title (3.9 g, 74percent) was obtained.
1H NMR (CDCl3): δ 8.63 (1H, d, J=4.8 Hz), 8.34 (1H, d, J=2.8 Hz), 8.16-8.14 (1H, m), 7.79-7.76 (1H, m), 7.62-7.60 (1H, m), 7.31-7.27 (1H, m), 7.11 (1H, d, J=9.2 Hz), 5.49 (2H, s).
52% With caesium carbonate; sodium iodide In acetonitrile at 60℃; for 5 h; 2-CHLORO-4-NITRO PHENOL 10G (57.6 MMOL, 1EQ), 2-PYCOLYL CHLORIDE hydrogen chloride 9.45g (57.6 mmol, 1 eq) cesium carbonate 41.3 (126.8 mmol, 2.2 eq) and sodium iodide 8. 64G (57.6 mmol, 1 eq) were suspended in 200 mL acetonitrile. The reaction mixture was stirred at 60°C for 5h. The resulted suspension was filtered and washed with 400 mL water, YIELDING 2- (2-CHLORO-4-NITRO-PHENOXYMETHYL)-PYRIDINE (8G, 52percent) as a red solid. 2- (2-CHLORO-4-NITRO-PHENOXYMETHYL)-PYRIDINE (8 g, 30. 2MMOL, 1 eq) and 8. 44g iron (151.1 mmol, 5 eq) were mixed in 100 mL acetic acid and 50 mL ethyl acetate and were stirred at rt overnight. The reaction mixture was filtered through celite pad. The filtrate was concentrated in vacuo and neutralized with sat. NA2CO3 solution. The solution was extracted with ethyl acetate and the organic layer was washed with brine and concentrated in vacuo. The resulting crude material was purified by flash chromatography eluting with 30percent ethyl acetate/hexane yielding 3. 2G of 3-Chloro-4- (pyridin-2-ylmethoxy)-phenylamine as a white solid (52percent). 1H-NMR (CDCL3) No. 5.18 (s, 2H), 6.50 (dd, 1H), 6.76 (d, 1H),. 6.80 (d, 1H), 7.22 (m, 1 H), 7.64 (d, 1H), 7.73 (td, 1H), 8.55 (m, 1H) ; LCMS RT = 0.89 min; [M+H]+= 235.1.
52% With caesium carbonate; sodium iodide In acetonitrile at 60℃; for 5 h; 2-chloro-4-nitro phenol 1Og (57.6 mmol, leq), 2-pycolyl chloride hydrogen chloride 9.45g (57.6 mmol, 1 equiv) cesium carbonate 41.3 (126.8 mmol, 2.2 equiv) and sodium iodide 8.64g (57.6 mmol, 1 equiv) were suspended in 200 mL acetonitrile. The reaction mixture was stirred at 60°C for 5h. The resulted suspension was filtered and washed with 400 mL water, yielding 2-(2-chloro-4-nitro-phenoxymethyl)-pyridine (8g, 52percent) as a red solid. 2-(2-chloro-4-nitro-phenoxymethyl)-pyridine (8 g, 30.2mmol, 1 equiv) and 8.44g iron (151.1 mmol, 5 equiv) were mixed in 100 mL acetic acid and 50 mL EtOAc and were stirred at rt overnight. The reaction mixture was filtered through a pad of Celite.(R).. The filtrate was concentrated in vacuo and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc and the organic layer was washed with brine and concentrated in vacuo. The resulting crude material was purified by flash chromatography eluting with EtOAc/hexane (3:7) to give 3-Chloro-4-(pyridin-2-ylmethoxy)-phenylamine (3.2 g, 52percent) as a white solid. 1H-NMR (CDCl3) δ 5.18 (s, 2H), 6.50 (dd, IH), 6.76 (d, IH),. 6.80 (d, IH), 7.22 (m, IH), 7.64 (d, IH), 7.73 (td, IH), 8.55 (m, IH); LCMS RT = 0.89 min; [M+H]+ = 235.1.
52% With caesium carbonate; sodium iodide In acetonitrile at 60℃; for 5 h; 2-chloro-4-nitro phenol (10 g, 57.6 mmol, 1 equiv), 2-pycolyl chloride hydrogen chloride (9.45 g, 57.6 mmol, 1 equiv), cesium carbonate 41.3 (126.8 mmol, 2.2 equiv) and sodium iodide (8.64 g, 57.6 mmol, 1 equiv) were suspended in 200 mL acetonitrile. The reaction mixture was stirred at 60° C. for 5 h. The resulted suspension was filtered and washed with water (400 mL), yielding 2-(2-chloro-4-nitro-phenoxymethyl)-pyridine (8 g, 52percent) as a red solid.
52% With caesium carbonate; sodium iodide In acetonitrile at 60℃; for 5 h; 2-Chloro-4-nitro phenol 10 g (57.6 mmol, 1 eq), 2-(chloromethyl)pyridine hydrogen chloride 9.45 g (57.6 mmol, 1 equiv), cesium carbonate (41.3 g, 126.8 mmol, 2.2 equiv) and sodium iodide 8.64 g (57.6 mmol, 1 equiv) were suspended in 200 mL acetonitrile. The reaction mixture was stirred at 60 0C for 5 h. The resulted suspension was filtered and washed with 400 mL water, yielding 2-(2-chloro-4-nitro-phenoxymethyl)-pyridine (8 g,52percent) as a red solid.

References: [1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 11, p. 3090 - 3104.
[2] Patent: US2016/214964, 2016, A1, . Location in patent: Paragraph 0138.
[3] Patent: WO2005/10008, 2005, A1, . Location in patent: Page/Page column 114-115.
[4] Patent: WO2006/23843, 2006, A2, . Location in patent: Page/Page column 64.
[5] Patent: US2010/298297, 2010, A1, . Location in patent: Page/Page column 14.
[6] Patent: WO2006/55268, 2006, A2, . Location in patent: Page/Page column 32.
[7] Research on Chemical Intermediates, 2013, vol. 39, # 7, p. 3105 - 3110.
[8] Patent: EP3181553, 2017, A1, . Location in patent: Paragraph 0209; 0210.
[9] European Journal of Medicinal Chemistry, 2018, vol. 155, p. 316 - 336.
 

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