Potassium Carbonate → t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate

HRID 909493Notes

Reaction equation

HRID 909493 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:22])[O:5][C:6]1[CH:7]=[C:8]([OH:21])[CH:9]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:11]=1.Br[C:24]1[N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:26]([C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[CH:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[OH:21][C:8]1[CH:9]=[C:10]([C:24]2[N:25]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C:26]([C:29]3[S:30][CH:31]=[CH:32][N:33]=3)=[CH:27][CH:28]=2)[CH:11]=[C:6]([O:5][C@@H:4]([CH3:22])[CH2:3][O:2][CH3:1])[CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 666811203-[(1S)-2-Methoxy-1-methylethoxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 66682601t-Butyl 2-bromo-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate

Product 1

HCID 66681373t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

3-[(1S)-2-Methoxy-1-methylethoxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (3.30 g, 10.7 mmol) synthesized in Example (38c) and t-butyl 2-bromo-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (4.10 g, 12.5 mmol) synthesized in Example (1g) were dissolved in a mixed solvent of 1,4-dioxane (100 mL) and water (25 mL), and [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane complex (400 mg, 0.490 mmol) and potassium carbonate (7.20 g, 52.1 mmol) were added, followed by stirring at 50° C. for 4 hours under nitrogen atmosphere. After the reaction solution was cooled to room temperature, water (200 mL) was added, and extraction was carried out with ethyl acetate (400 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=25%-40%) to afford the desired compound (3.72 g, yield 81%) as a pale yellow oil.

Workup

  1. additionwere added
  2. temperatureAfter the reaction solution was cooled to room temperature
  3. extractionextraction
  4. washThe organic layer was washed with saturated brine
  5. dry with materialsubsequently dried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified
  8. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=25%-40%)

Sources & evidence

ORD record
ord-ce0ce94cb924428b90bbeab6e669d729
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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