Thionyl Chloride → 2-(Chloromethyl)-3-fluoropyridine

HRID 545558Notes

Reaction equation

HRID 545558 reaction equation
[F:1][C:2]1[C:3]([CH2:8]O)=[N:4][CH:5]=[CH:6][CH:7]=1.S(Cl)([Cl:12])=O.C(=O)(O)[O-].[Na+]>ClCCl.[Cl-].[Na+].O>[Cl:12][CH2:8][C:3]1[C:2]([F:1])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 19703803(3-Fluoropyridin-2-yl)methanol

Product 1

HCID 151336022-(Chloromethyl)-3-fluoropyridineYield 80.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve (3-fluoro-pyridin-2-yl)-methanol (215 mg, 1.69 mmol) in dichloromethane (10 mL) and cool to 0° C. Add thionyl chloride (160 μL, 2.20 mmol) and stir the reaction for one hour. Add dichloromethane (50 mL) and stir the reaction with saturated aqueous sodium bicarbonate (2×40 mL) and brine (2×40 mL). Separate and dry the organic portion over magnesium sulfate, filter, and concentrate under reduced pressure to provide 198 mg (80%) of product, which is used without further purification. MS: m/z 146, 148 [C6H5ClFN+1]+; 1H NMR (300 MHz, CDCl3): δ 8.41-8.44 (m, 1H), 7.41-7.47 (m, 1H), 7.28-7.34 (m, 1H), 4.75 (d, J=2.0 Hz, 2H); 19F NMR (282 MHz, CDCl3): δ-123.8.

Workup

  1. customthe reaction for one hour
  2. customSeparate
  3. dry with materialdry the organic portion over magnesium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-a725570d0d074759ae422089a7a3290f
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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