Cesium carbonate → 3-methyl-N-[3-(pentafluoroethyl)phenyl]-5-(1,3-thiazol-5-yl)aniline

HRID 1039906Notes

Reaction equation

HRID 1039906 reaction equation
Cl[C:2]1N=[C:6]([C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:4][N:3]=1.[CH3:15][C:16]1[CH:17]=C([CH:20]=[C:21]([C:23]2[S:27][CH:26]=[N:25][CH:24]=2)[CH:22]=1)N.[CH3:28][C:29]1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:30]1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:15][C:16]1[CH:17]=[C:2]([CH:20]=[C:21]([C:23]2[S:27][CH:26]=[N:25][CH:24]=2)[CH:22]=1)[NH:3][C:4]1[CH:30]=[CH:29][CH:28]=[C:6]([C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10])[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58456365HCID 58456365, compoundHCID 866582362-Chloro-4-(pentafluoroethyl)pyrimidine

Product 1

HCID 866582353-methyl-N-[3-(pentafluoroethyl)phenyl]-5-(1,3-thiazol-5-yl)anilineYield 86.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-4-(pentafluoroethyl)pyrimidine (61 mg, 0.26 mmol) and 3-methyl-5-(1,3-thiazol-5-yl)aniline (50 mg, 0.26 mmol) in degassed 1,4-dioxane (1.1 mL) were added Xantphos (23 mg, 0.039 mmol), Pd(OAc)2 (5.9 mg, 0.026 mmol) and Cs2CO3 (172 mg, 0.53 mmol) and the reaction was heated to 100° C. for 30 minutes. After cooling, the reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate. The layers were separated and the aqueous phase was extracted EtOAc (10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (10 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Purification on silica (20-60% ethyl acetate in hexanes) afforded 3-methyl-N-[3-(pentafluoroethyl)phenyl]-5-(1,3-thiazol-5-yl)aniline (13 mg, 13%) as a colorless foam. MS ESI: [M+H]+ m/z 387.0.

Workup

  1. temperatureAfter cooling
  2. customthe reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted EtOAc (10 mL)
  5. washThe combined organic phases were washed with saturated aqueous sodium chloride (10 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification on silica (20-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-dcad3f042072443ca4bed0e8137b1bb5
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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