Hydrochloric Acid → 2-(Chloromethyl)-5-fluoropyridine hydrochloride

HRID 545554Notes

Reaction equation

HRID 545554 reaction equation
S(Cl)([Cl:3])=O.[F:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:12]O)=[N:10][CH:11]=1.C(=O)(O)[O-].[Na+].[ClH:19]>C(Cl)Cl>[ClH:3].[Cl:19][CH2:12][C:9]1[CH:8]=[CH:7][C:6]([F:5])=[CH:11][N:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 24729312(5-Fluoropyridin-2-yl)methanol

Product 1

HCID 574316752-(Chloromethyl)-5-fluoropyridine hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add thionyl chloride (320 μL, 4.30 mmol) slowly to a 0° C. solution of (5-fluoro-pyridin-2-yl)-methanol (420 mg, 3.31 mmol) in methylene chloride (15 mL). Stir the reaction at 0° C. for 3 h and quench with isopropyl alcohol. Dilute the reaction contents with methylene chloride (50 mL) and then saturated aqueous sodium bicarbonate (20 mL). Separate the organic phase, dry(magnesium sulfate), filter and concentrate in vacuo to give an oil. The oil is treated with hydrochloric acid (10 mL, 3 M solution in dioxane) at room temperature for 30 min. The resultant solid is collected by filtration and washed with a minimal amount of cold diethyl ether to give 200 mg (33%) as a yellow solid. MS (APCI): m/z 146 [C6H5ClFN+H]+; 1H NMR (300 MHz, CDCl3): δ 8.42 (s, 1H), 7.56-7.37 (m, 2H), 4.67 (s, 2H).

Workup

  1. customthe reaction at 0° C. for 3 h
  2. customquench with isopropyl alcohol
  3. additionDilute
  4. customthe reaction contents with methylene chloride (50 mL)
  5. customSeparate the organic phase, dry(magnesium sulfate)
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customto give an oil
  9. filtrationThe resultant solid is collected by filtration
  10. washwashed with a minimal amount of cold diethyl ether
  11. customto give 200 mg (33%) as a yellow solid

Sources & evidence

ORD record
ord-4de803d1f2064be6990456de3b78feb3
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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