Potassium Carbonate → 2-Benzyl 1-t-butyl 5-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrole-1,2-dicarboxylate

HRID 1964607Notes

Reaction equation

HRID 1964607 reaction equation
Br[C:2]1[N:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C:5]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])=[CH:4][CH:3]=1.[CH3:24][O:25][CH2:26][C@H:27]([CH3:45])[O:28][C:29]1[CH:30]=[C:31]([OH:44])[CH:32]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:34]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[OH:44][C:31]1[CH:32]=[C:33]([C:2]2[N:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C:5]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])=[CH:4][CH:3]=2)[CH:34]=[C:29]([O:28][C@@H:27]([CH3:45])[CH2:26][O:25][CH3:24])[CH:30]=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 666830832-Benzyl 1-t-butyl 5-bromo-1H-pyrrole-1,2-dicarboxylate

Product 1

HCID 866495672-Benzyl 1-t-butyl 5-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-1H-pyrrole-1,2-dicarboxylateYield 75.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
55 °C

Procedure

2-Benzyl 1-t-butyl 5-bromo-1H-pyrrole-1,2-dicarboxylate (8.75 g, 23.0 mmol) synthesized in Example (66b) and 3-[(1S)-2-methoxy-1-methylethoxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (7.11 g, 23.1 mmol) synthesized in Example (38c) were dissolved in a mixed solvent of 1,4-dioxane (92 mL) and water (23 mL), and [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane complex (570 mg, 0.698 mmol) and potassium carbonate (7.95 g, 57.5 mmol) were added, followed by stirring at 55° C. for 3 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 (200 mL). The organic layer was washed with saturated brine, and subsequently dried over anhydrous sodium 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=15%-35%) to afford the desired compound (8.32 g, yield 75%) as a brown 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 sodium 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=15%-35%)

Sources & evidence

ORD record
ord-93abaf12c5054cd2a1a2426002372eec
Source dataset
uspto-grants-2013_04
Patent number
US08415359B2

Reaction notes

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