Potassium Carbonate → t-Butyl 2-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate

HRID 909422Notes

Reaction equation

HRID 909422 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:32])[O:5][C:6]1[CH:7]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=2)[CH:11]=1.Br[C:34]1[N:35]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:36]([C:39]2[S:40][CH:41]=[CH:42][N:43]=2)=[CH:37][CH:38]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[CH3:1][O:2][CH2:3][C@H:4]([CH3:32])[O:5][C:6]1[CH:7]=[C:8]([C:34]2[N:35]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[C:36]([C:39]3[S:40][CH:41]=[CH:42][N:43]=3)=[CH:37][CH:38]=2)[CH:9]=[C:10]([O:12][C:13]2[CH:14]=[CH:15][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:17][CH:18]=2)[CH:11]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 666813752-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 66682601t-Butyl 2-bromo-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate

Product 1

HCID 66682326t-Butyl 2-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

2-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[4-(methylsulfonyl)phenoxy]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (6.44 g, 13.9 mmol) synthesized in Example (1e) and t-butyl 2-bromo-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (5.21 g, 15.8 mmol) synthesized in Example (1g) were dissolved in a mixed solvent of 1,4-dioxane (200 mL) and water (50 mL), and [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane complex (564 mg, 0.691 mmol) and potassium carbonate (9.67 g, 70.0 mmol) were added, followed by stirring at 50° 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 (400 mL). The organic layer was washed with saturated brine, and subsequently dried over 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=30%-50%) to afford the desired compound (7.12 g, yield 88%) 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 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=30%-50%)

Sources & evidence

ORD record
ord-e44e527ee7154b9a89804fdc54d4e1b3
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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