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

HRID 1639693Notes

Reaction equation

HRID 1639693 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[N:12]1[C:16]([NH2:17])=[C:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24]C)=[CH:20][CH:19]=2)[N:14]=[N:13]1.B(Br)(Br)Br.CO.[OH-].[Na+]>ClCCl.O>[NH2:17][C:16]1[N:12]([C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]=2[F:1])[N:13]=[N:14][C:15]=1[C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 25134Boron tribromideHCID 252156773-(2-Fluoro-4-trifluoromethyl-phenyl)-5-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamine

Product 1

HCID 1359494924-[5-Amino-1-(2-fluoro-4-trifluoromethyl-phenyl)-1H-[1,2,3]triazol-4-yl]-phenolYield 91.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 3-(2-fluoro-4-trifluoromethyl-phenyl)-5-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamine (14) (0.400 g, 1.1354 mmol) in anhydrous dichloromethane (25 ml), cooled to −78° C. and under a nitrogen flow, a solution of boron tribromide (1.991 g, ˜0.75 ml, 7.9478 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 5 min stirring, 10% sodium hydroxide solution (10 ml) is added and the aqueous layer, once separated, is acidified with 10% hydrochloric acid solution and extracted with chloroform (3×70 ml). The combined organic layers are dried over MgSO4, filtered and evaporated to afford a solid residue (0.350 g). This is purified by column chromatography over silica gel (60-120 mesh) eluting with 16% ethyl acetate in hexane (0.150 g, 40% yield). M.p. 163.5-165.2° C. LC-ESI-HRMS of [M+H]+ shows 339.0853 Da. Calc. 339.086898 Da, dev. −4.7 ppm.

Workup

  1. temperatureit is then cooled again in an ice-salt bath
  2. customthe aqueous layer, once separated
  3. extractionextracted with chloroform (3×70 ml)
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-96f4ea68ed9a47468b011e88a2ae67fc
Source dataset
uspto-grants-2012_02
Patent number
US08110588B2

Reaction notes

Loading…