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Phosphorus oxychloride → 2-Chloro-5-(chloromethyl)-3-(trifluoromethyl)pyridine

HRID 2274064
Notes
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Reaction equation

HRID 2274064 reaction equation
[Cl:1][CH2:2][C:3]1[CH:4]=[C:5]([C:11]([F:14])([F:13])[F:12])[C:6](OC)=[N:7][CH:8]=1.O=P(Cl)(Cl)[Cl:17]>CN(C=O)C>[Cl:17][C:6]1[C:5]([C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]([CH2:2][Cl:1])=[CH:8][N:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 534390555-(Chloromethyl)-2-methoxy-3-(trifluoromethyl)pyridine

Product 1

HCID 116155492-Chloro-5-(chloromethyl)-3-(trifluoromethyl)pyridineYield 65.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a cold solution of 5-(chloromethyl)-2-methoxy-3-(trifluoromethyl)pyridine (0.3 g, 1.33 mmol) in DMF (0.6 mL) was added dropwise POCl3 (1.02 g, 6.65 mmol). The reaction was stirred for 1 h at 100° C. in a sealed tube. The reaction was cooled to room temperature, and poured onto ice water (10 mL). The reaction was extracted with DCM (thrice) and the combined organic layer was washed with water and brine, dried with MgSO4 and concentrated. The residue was purified by silica gel column chromatography to provide the title compound (0.20 g). LCMS m/z=230.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 4.62 (s, 2H), 8.06 (d, J=2.3 Hz, 1H), 8.57 (d, J=2.3 Hz, 1H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. additionpoured onto ice water (10 mL)
  3. extractionThe reaction was extracted with DCM (thrice)
  4. washthe combined organic layer was washed with water and brine
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b1ffeb0d845a4694973cfbac2811b408
Source dataset
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09126932B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes