Ethanol → 2-({5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino}-1-methyl-4-[4-(trifluoromethyl)phenyl]-1H-pyrazol-3-yl}oxy)ethyl Acetate

HRID 1062785Notes

Reaction equation

HRID 1062785 reaction equation
[C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12](I)=[C:11]([N:14]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])[N:10]([CH3:34])[N:9]=1)(=[O:3])[CH3:2].C(O)C.C(=O)([O-])[O-].[Cs+].[Cs+].[F:44][C:45]([F:56])([F:55])[C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1>C1(C)C=CC=CC=1.O>[C:1]([O:4][CH2:5][CH2:6][O:7][C:8]1[C:12]([C:49]2[CH:50]=[CH:51][C:46]([C:45]([F:56])([F:55])[F:44])=[CH:47][CH:48]=2)=[C:11]([N:14]([S:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:15][O:16][CH2:17][CH2:18][O:19][CH3:20])[N:10]([CH3:34])[N:9]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 10796Cesium carbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 222818952-[(5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino)-4-iodo-1-methyl-1H-pyrazol-3-yl)oxy]ethyl acetate

Product 1

HCID 222819502-({5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino}-1-methyl-4-[4-(trifluoromethyl)phenyl]-1H-pyrazol-3-yl}oxy)ethyl Acetate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To 2-[(5-{{[4-(tert-butyl)phenyl]sulfonyl}[(2-methoxyethoxy)methyl]amino)-4-iodo-1-methyl-1H-pyrazol-3-yl)oxy]ethyl acetate (Preparation 14) (300 mg) in solution in toluene (5 ml) were successively added ethanol (1 ml), cesium carbonate (805 mg) in water (2 ml), and 4-(trifluoromethyl)phenylboronic acid (187 mg) at room temperature. The reaction mixture was degassed (vacuum followed by nitrogen atmosphere). This operation was repeated 5 times. The tetrakis(triphenylphosphine)-palladium(0) (15 mg) was then added and the reaction mixture degassed twice. The reaction mixture was refluxed for 1.5 hours and then cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate (20 ml) and a saturated solution of sodium carbonate (20 ml). The organic layer was separated and washed with a saturated solution of sodium carbonate (10 ml) and then brine (10 ml). The solution was dried on magnesium sulfate, the solution filtered on celite and concentrated under reduced pressure. The crude material was purified by chromatography on a suction column packed with silica eluted with ethyl acetate:hexane (1:2 to 3:1 gradually) to yield the desired product as an off white solid (200 mg).

Workup

  1. customat room temperature
  2. customThe reaction mixture was degassed (vacuum followed by nitrogen atmosphere)
  3. additionThe tetrakis(triphenylphosphine)-palladium(0) (15 mg) was then added
  4. customthe reaction mixture degassed twice
  5. temperatureThe reaction mixture was refluxed for 1.5 hours
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was partitioned between ethyl acetate (20 ml)
  8. customThe organic layer was separated
  9. washwashed with a saturated solution of sodium carbonate (10 ml)
  10. customThe solution was dried on magnesium sulfate
  11. filtrationthe solution filtered on celite
  12. concentrationconcentrated under reduced pressure
  13. customThe crude material was purified by chromatography on a suction column
  14. washeluted with ethyl acetate:hexane (1:2 to 3:1 gradually)

Sources & evidence

ORD record
ord-5721f6b76aca40d99b0fddf24a1ca8bd
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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