Thionyl Chloride → 5-[5-(Chloromethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrile

HRID 517727Notes

Reaction equation

HRID 517727 reaction equation
S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[N:11]([C:12]2[CH:13]=[CH:14][C:15]([C:20]([F:23])([F:22])[F:21])=[C:16]([CH:19]=2)[C:17]#[N:18])[N:10]=[N:9][N:8]=1>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:3][CH2:6][C:7]1[N:11]([C:12]2[CH:13]=[CH:14][C:15]([C:20]([F:23])([F:22])[F:21])=[C:16]([CH:19]=2)[C:17]#[N:18])[N:10]=[N:9][N:8]=1

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 866918745-[5-(Hydroxymethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrile2×

Product 1

HCID 866918755-[5-(Chloromethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrileYield 521%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Thionyl chloride (4.25 g, 3.57 mmol) was added dropwise to a solution of 5-[5-(hydroxymethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrile (Intermediate 40, 8.0 g, 29.7 mmol) in toluene (200 mL) at 0° C. The reaction mixture was allowed to warm to room temperature and then heated to reflux for 4 hr. The mixture was diluted with EtOAc and washed with ice-water, and saturated NaHCO3, dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford the crude product. This was purified by column chromatography (100-200 mesh silica gel), eluting with 20%-40% ethyl acetate/pet ether to give the title compound (5.35 g) as a white powder.

Workup

  1. temperatureheated
  2. temperatureto reflux for 4 hr
  3. washwashed with ice-water, and saturated NaHCO3
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude product
  7. customThis was purified by column chromatography (100-200 mesh silica gel)
  8. washeluting with 20%-40% ethyl acetate/pet ether

Sources & evidence

ORD record
ord-d144f58b81694ad79ff787bb381469f7
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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