Potassium Phosphate, Tribasic → 5-(2,2-Difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyridin-2-amine

HRID 2272203Notes

Reaction equation

HRID 2272203 reaction equation
Br[C:2]1[C:12]([CH3:13])=[CH:11][C:5]2[O:6][C:7]([F:10])([F:9])[O:8][C:4]=2[CH:3]=1.ClC1C=CC(C(F)(F)F)=CC=1OC1[CH:19]=[CH:20][C:21]([N+:24]([O-])=O)=[N:22][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:44]1.C(#N)C.O>>[F:9][C:7]1([F:10])[O:8][C:4]2[CH:3]=[C:2]([CH3:44])[C:12]([C:13]3[CH:19]=[CH:20][C:21]([NH2:24])=[N:22][CH:23]=3)=[CH:11][C:5]=2[O:6]1

Participants

5

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 584867835-Bromo-2,2-difluoro-6-methylbenzo[d][1,3]dioxoleHCID 671268785-(2-Chloro-5-(trifluoromethyl)phenoxy)-2-nitropyridineHCID 67448433Dioxane acetonitrile water

Product 1

HCID 584866525-(2,2-Difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyridin-2-amineYield 90%

Conditions

Temperature
90 °C

Procedure

Palladium tetrakis-triphenylphosphine (58 mg, 43 μmol) was added to a degassed solution of bromide 2 (250 mg, 1.0 mmol) and boronate 3 (274 mg, 1.25 mmol) in dioxane: acetonitrile:water (9:9:2, 5 mL) and potassium phosphate (317 mg, 1.5 mmol). The resulting mixture was heated under argon at 90° C. with stirring for 14 hours. The mixture was then cooled, extracted with dichloromethane (3×50 mL), dried with sodium sulfate and concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-50% ethyl acetate in hexane) provided 4 (236 mg, 90%) as an crystalline solid: LRESIMS m/z 265.2 [M+H]+, calcd. for C13H11F2N2O2 265.1.

Workup

  1. temperatureThe mixture was then cooled
  2. extractionextracted with dichloromethane (3×50 mL)
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-829b1cceb68548f2b80d450450e14010
Source dataset
uspto-grants-2015_09
Patent number
US09120751B2

Reaction notes

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