Propiolic Acid → Cgp-47292

HRID 335511Notes

Reaction equation

HRID 335511 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[F:5][C:6]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[C:7]=1[CH2:8]Cl.[C:15]([OH:19])(=[O:18])[C:16]#[CH:17].[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OC(C)C)(=O)C.O>[F:5][C:6]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[C:7]=1[CH2:8][N:1]1[CH:17]=[C:16]([C:15]([OH:19])=[O:18])[N:3]=[N:2]1

Participants

8

Reactant 4

HCID 10110Propiolic AcidHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 5815702,6-Difluorobenzyl chloride

Product 1

HCID 10014469Cgp-47292Yield 58.4%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
22.5 °C

Procedure

A suspension of 10.25 g (158 mmol) of NaN3, 2.5 g (7.76 mmol) of tetrabutylammonium bromide and 25 g (154 mmol) of 2,6-difluorobenzyl chloride in 50 mL of isopropyl acetate was left stirring at 20-25° C. during 14 h until showing completion by TLC. The resultant mixture was washed with 10% NaCl aqueous solution at 0° C. to remove unreacted NaN3 and the organic phase was stirred with a solution of 17.26 g (246 mmol) of propiolic acid in 50 mL of water at 50° C. during 8 h. After cooling to 20-25° C., the pH was adjusted to 3.2-3.4 by addition of 30% aqueous solution of NaOH and, after one hour at 20-25° C., the suspension was filtered. The solid was further washed with 25 mL of isopropyl acetate precooled at 0-5° C., washed with 40 mL of water dried at 200 mbar and 50° C. to obtain 21.52 g (57.4%) of 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid (purity by UPLC area: 99.94%, 3H-isomer: 0.06%).

Workup

  1. waitwas left
  2. washThe resultant mixture was washed with 10% NaCl aqueous solution at 0° C.
  3. customto remove unreacted NaN3
  4. temperatureAfter cooling to 20-25° C.
  5. filtrationthe suspension was filtered
  6. washThe solid was further washed with 25 mL of isopropyl acetate
  7. customprecooled at 0-5° C.
  8. washwashed with 40 mL of water
  9. customdried at 200 mbar and 50° C.

Sources & evidence

ORD record
ord-3c602c39549c49dab298337ebfc71b73
Source dataset
uspto-grants-2014_11
Patent number
US08884026B2

Reaction notes

Loading…