Potassium Phosphate, Tribasic → 5-(6-chloro-2-fluoropyridin-3-yl)-1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazole

HRID 2281038Notes

Reaction equation

HRID 2281038 reaction equation
FC(F)(F)S(O[C:7]1[CH:19]=[CH:18][C:10]2[N:11]([CH2:14][CH:15]3[CH2:17][CH2:16]3)[N:12]=[N:13][C:9]=2[C:8]=1[C:20]([F:23])([F:22])[F:21])(=O)=O.[Cl:26][C:27]1[N:32]=[C:31]([F:33])[C:30](B(O)O)=[CH:29][CH:28]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Cl:26][C:27]1[N:32]=[C:31]([F:33])[C:30]([C:7]2[CH:19]=[CH:18][C:10]3[N:11]([CH2:14][CH:15]4[CH2:16][CH2:17]4)[N:12]=[N:13][C:9]=3[C:8]=2[C:20]([F:21])([F:22])[F:23])=[CH:29][CH:28]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 46739261(6-Chloro-2-fluoropyridin-3-yl)boronic acidHCID 867119761-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl trifluoromethanesulfonate

Product 1

HCID 867119775-(6-chloro-2-fluoropyridin-3-yl)-1-(cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazole

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(Cyclopropylmethyl)-4-(trifluoromethyl)-1H-benzotriazol-5-yl trifluoromethanesulfonate (221 mg, 0.568 mmol) and (6-chloro-2-fluoropyridin-3-yl)boronic acid (130 mg, 0.738 mmol, 1.3 equiv) were dissolved in degassed dioxane (5.6 mL) and treated with potassium phosphate (0.37 mL, 2 M aqueous, 0.74 mmol, 1.3 equiv) and palladium tetrakis(triphenylphosphine) (98 mg, 0.085 mmol, 0.15 equiv). The mixture was placed into a preheated oil bath at 90° C. for 3 hours, cooled to ambient temperature, diluted with ethyl acetate (40 mL) and washed with sodium bicarbonate (2×30 mL, aqueous saturated). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 70:30; hexanes:ethyl acetate), providing the titled compound.

Workup

  1. washwashed with sodium bicarbonate (2×30 mL, aqueous saturated)
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel gradient chromatography (100:0 to 70:30; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-60c54ec3960e4d31825a6730e007f312
Source dataset
uspto-grants-2015_09
Patent number
US09139576B2

Reaction notes

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