Methanol → 4-[5-Amino-4-(2-fluoro-4-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-phenol

HRID 1639695Notes

Reaction equation

HRID 1639695 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[N:16]=[N:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23]C)=[CH:19][CH:18]=2)[C:13]=1[NH2:25].B(Br)(Br)Br.CO.[OH-].[Na+]>ClCCl.O>[NH2:25][C:13]1[N:14]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[N:15]=[N:16][C:12]=1[C:3]1[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]=1[F:1]

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 25134Boron tribromideHCID 252159065-(2-Fluoro-4-trifluoromethyl-phenyl)-3-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamine

Product 1

HCID 252159074-[5-Amino-4-(2-fluoro-4-trifluoromethyl-phenyl)-[1,2,3]triazol-1-yl]-phenolYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 5-(2-fluoro-4-trifluoromethyl-phenyl)-3-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamine (16) (0.450 g, 1.2774 mmol) in anhydrous dichloromethane (15 ml), cooled to −78° C. and under a nitrogen flow, a solution of boron tribromide (2.240 g, ˜0.84 ml, 8.9418 mmol) in 5 ml of anhydrous dichloromethane is added drop-wise. The mixture is allowed to reach room temperature spontaneously overnight and it is then cooled again in an ice-salt bath and the excess of the reagent is decomposed upon drop-wise addition of 10 ml of methanol and 10 ml of water. After 10 min stirring, 10% sodium hydroxide solution (15 ml) is added and the aqueous layer, once separated, is acidified with 10% hydrochloric acid solution and extracted with chloroform (3×50 ml). The combined organic layers are dried over MgSO4, filtered and evaporated to afford a solid residue (0.380 g, 88% yield, 99.71% pure at HPLC). M.p. 176.2-177.5° C. LC-ESI-HRMS of [M+H]+ shows 339.0854 Da. Calc. 339.086898 Da, dev. −4.4 ppm.

Workup

  1. temperatureit is then cooled again in an ice-salt bath
  2. customthe aqueous layer, once separated
  3. extractionextracted with chloroform (3×50 ml)
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford a solid residue (0.380 g, 88% yield, 99.71% pure at HPLC)

Sources & evidence

ORD record
ord-9fcb2f4631e349e6bcb11d118c558b7c
Source dataset
uspto-grants-2012_02
Patent number
US08110588B2

Reaction notes

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