Hydrochloric Acid → 1-[5-(2H-Tetrazol-5-yl)-1,3,4-thiadiazol-2-yl}-4-[2-(trifluoromethyl)phenoxy]piperidine

HRID 561193Notes

Reaction equation

HRID 561193 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:22]=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[S:16][C:15]([C:17]#[N:18])=[N:14][N:13]=2)[CH2:8][CH2:7]1.[N-:25]=[N+:26]=[N-:27].[Na+].Cl.[NH+]1C=CC=CC=1.Cl>CN1C(=O)CCC1>[N:18]1[NH:25][N:26]=[N:27][C:17]=1[C:15]1[S:16][C:12]([N:9]2[CH2:10][CH2:11][CH:6]([O:5][C:4]3[CH:19]=[CH:20][CH:21]=[CH:22][C:3]=3[C:2]([F:1])([F:23])[F:24])[CH2:7][CH2:8]2)=[N:13][N:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 33557Sodium AzideHCID 21584435Pyridinium hydrochlorideHCID 533885255-{4-[2-(Trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazole-2-carbonitrile

Product 1

HCID 159806391-[5-(2H-Tetrazol-5-yl)-1,3,4-thiadiazol-2-yl}-4-[2-(trifluoromethyl)phenoxy]piperidine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 5-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-1,3,4-thiadiazole-2-carbonitrile (4.99 g, 14.1 mmol), NaN3 (4.65 g, 71.5 mmol) and pyridinium hydrochloride (3.43 g, 29.7 mmol) in NMP (50 mL) was heated at 130° C. for 18 h. The reaction mixture was cooled to room temperature and poured into aqueous 0.5 N HCl, extracted with EtOAc, washed three times with aqueous 0.5 N HCl, and with aqueous brine solution. The organic layer was dried (Na2SO4) and filtered. Evaporation of the solvent was followed by trituration in a mixture of MeOH/Et2O/heptane (1:1:6) (v/v) with stirring for 4 h at room temperature. After this time, the suspension was cooled with an ice-water bath and the title compound was collected by filtration as a white solid. The material was dried under high vacuum by heating at 50° C. for 1-2 h.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. washwashed three times with aqueous 0.5 N HCl
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customEvaporation of the solvent
  7. additionwas followed by trituration in a mixture of MeOH/Et2O/heptane (1:1:6) (v/v)
  8. temperatureAfter this time, the suspension was cooled with an ice-water bath
  9. filtrationthe title compound was collected by filtration as a white solid
  10. customThe material was dried under high vacuum
  11. temperatureby heating at 50° C. for 1-2 h.

Sources & evidence

ORD record
ord-45b7f743e6d849329f9e563d55a1e0b9
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

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