Hydrochloric Acid → 4-[5-(1-piperazinylmethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrile

HRID 517783Notes

Reaction equation

HRID 517783 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([CH2:14][N:15]3[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]3)=[N:12][N:11]=[N:10]2)=[CH:5][C:4]=1[C:28]([F:31])([F:30])[F:29])#[N:2].Cl.O1CCOCC1>CO>[N:15]1([CH2:14][C:13]2[N:9]([C:6]3[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:28]([F:31])([F:29])[F:30])[CH:5]=3)[N:10]=[N:11][N:12]=2)[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66654416HCID 66654416, compound2×

Product 1

HCID 666545664-[5-(1-piperazinylmethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrileYield 97.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-({1-[4-cyano-3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)-1-piperazinecarboxylate (Intermediate 25, 532 mg, 1.22 mmol) in methanol (8 mL) was added hydrochloric acid in dioxane (5 mL, 20.0 mmol). The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated, the white solid was dissolved in methanol and poured onto a 5 g SCX cartridge, washed with methanol (2 CV) and eluted with 10% ammonia) in methanol (2 CV). The ammonia in methanol fraction was concentrated under vacuum to leave a white solid, 4-[5-(1-piperazinylmethyl)-1H-tetrazol-1-yl]-2-(trifluoromethyl)benzonitrile (402 mg).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe white solid was dissolved in methanol
  3. additionpoured onto a 5 g SCX cartridge
  4. washwashed with methanol (2 CV)
  5. washeluted with 10% ammonia) in methanol (2 CV)
  6. concentrationThe ammonia in methanol fraction was concentrated under vacuum

Sources & evidence

ORD record
ord-db8bc7ba5c574b1f90bc2b2237fbd2ac
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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