Thionyl Chloride → 2-(Chloromethyl)-4-fluoro-1-methoxybenzene

HRID 30318Notes

Reaction equation

HRID 30318 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH3:11])=[C:6]([CH2:8]O)[CH:7]=1.O=S(Cl)[Cl:14]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][CH3:11])=[C:6]([CH:7]=1)[CH2:8][Cl:14]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 22014996(5-Fluoro-2-methoxyphenyl)methanol

Product 1

HCID 3026862-(Chloromethyl)-4-fluoro-1-methoxybenzeneYield 61%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Neat (5-Fluoro-2-methoxy-phenyl)-methanol (19.587 g, 1 equiv.) is added to neat SOCl2 (42.2 mL, 4.6 equiv.) at −78° C. under a nitrogen atmosphere and the solution is then allowed to warm to room temperature and stirred until evolution of gas ceases. An equivalent volume of anhydrous toluene is added to the flask and the solution heated to 60° C. On cooling, the reaction solution is poured onto ice water. The toluene layer is separated and dried (MgSO4) and the solvent removed under reduced pressure. The crude material is sublimed (60-80° C./0.05 mBarr) to give the title compound as a white solid (13.40 g, 61%). MW 174.60; C8H8ClFO; 1H NMR (CDCl3): 3.87 (s, 3H), 4.60 (s, 2H), 6.79-7.20 (m, 3H).

Workup

  1. temperaturethe solution heated to 60° C
  2. temperatureOn cooling
  3. additionthe reaction solution is poured onto ice water
  4. customThe toluene layer is separated
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed under reduced pressure
  7. custom(60-80° C./0.05 mBarr)

Sources & evidence

ORD record
ord-022aabb333cd487794e3478b9e8ef063
Source dataset
uspto-grants-2008_09
Patent number
US07423037B2

Reaction notes

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