Sodium hydride → 4-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}-3-methylbenzaldehyde

HRID 909513Notes

Reaction equation

HRID 909513 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:14]2[N:15](C(OC(C)(C)C)=O)[C:16]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)=[CH:17][CH:18]=2)[CH:5]=[C:6]([O:8][C@@H:9]([CH3:13])[CH2:10][O:11][CH3:12])[CH:7]=1.F[C:32]1[CH:39]=[CH:38][C:35]([CH:36]=[O:37])=[CH:34][C:33]=1[CH3:40].[H-].[Na+].[Cl-].[NH4+]>CS(C)=O>[CH3:12][O:11][CH2:10][C@H:9]([CH3:13])[O:8][C:6]1[CH:7]=[C:2]([CH:3]=[C:4]([C:14]2[NH:15][C:16]([C:19]3[S:20][CH:21]=[CH:22][N:23]=3)=[CH:17][CH:18]=2)[CH:5]=1)[O:1][C:32]1[CH:39]=[CH:38][C:35]([CH:36]=[O:37])=[CH:34][C:33]=1[CH3:40]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 27348744-Fluoro-3-methylbenzaldehydeHCID 66681373t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate

Product 1

HCID 580654454-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[5-(1,3-thiazol-2-yl)-1H-pyrrol-2-yl]phenoxy}-3-methylbenzaldehydeYield 54%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

t-Butyl 2-{3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]phenyl}-5-(1,3-thiazol-2-yl)-1H-pyrrole-1-carboxylate (150 mg, 0.348 mmol) synthesized in Example (38d) and commercially available 4-fluoro-3-methylbenzaldehyde (0.14 mL, 1.148 mmol) were dissolved in dimethyl sulfoxide (5.0 mL), and sodium hydride (60%, 40 mg, 1.00 mmol) was added, followed by stirring at 100° C. for 4 hours under nitrogen atmosphere. The reaction solution was cooled to room temperature, a saturated aqueous ammonium chloride solution (30 mL) was added, and extraction was carried out with diethyl ether (30 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%-30%) to afford the desired compound (84 mg, yield 54%) as a yellow solid.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextraction
  3. washThe organic layer was washed with saturated brine
  4. dry with materialsubsequently dried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe resulting residue was purified
  7. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=25%-30%)

Sources & evidence

ORD record
ord-c9c764c922df43beb5186a66f06c6354
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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