HCID 21058511, compound → HCID 21945718, compound

HRID 2216921Notes

Reaction equation

HRID 2216921 reaction equation
C([O:8][C:9]([C:11]1[NH:12][C:13]([CH3:24])=[C:14]([CH2:17][CH2:18][CH2:19][O:20][C:21](=[O:23])[CH3:22])[C:15]=1[CH3:16])=[O:10])C1C=CC=CC=1>C1COCC1.[Pd]>[C:21]([O:20][CH2:19][CH2:18][CH2:17][C:14]1[C:15]([CH3:16])=[C:11]([C:9]([OH:10])=[O:8])[NH:12][C:13]=1[CH3:24])(=[O:23])[CH3:22]

Participants

4

Reactant 1

HCID 21058511HCID 21058511, compound

Product 1

HCID 21945718HCID 21945718, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4-(3-Acetoxypropyl)-3,5-dimethylpyrrole-2-carboxylic acid benzyl ester, the compound of formula (5) (18.6 g, 56.6 mmol), was dissolved in dry THF (440 mL), and 10% palladium on carbon (1.3 g) was added to the solution under a nitrogen stream. The reaction flask was evacuated until the solvent began to boil, and it was then backfilled with nitrogen (3×). The reaction flask was again evacuated until the solvent began to boil and was backfilled with hydrogen gas (5×). The reaction was then allowed to stir under hydrogen gas overnight. The resulting suspension was filtered to remove the palladium/carbon, and THF was added to redissolve the solids. Most of the THF was evaporated off, after which hexanes were added dropwise, with stirring, to the solution, causing a white solid to precipitate out. The solids were filtered, rinsed with hexanes, and dried overnight under vacuum to give 4-(3-acetoxypropyl)-3,5-dimethylpyrrole-2-carboxylic acid, the compound of formula (6) as a white crystalline powder (12.8 g, 94.2% yield). This compound (12.1 g, 50.2 mmol) was slurried in triethylorthoformate (60 mL), and the slurry cooled to 0° C. in an ice/brine bath. Trifluoroacetic acid (60 mL) was added while maintaining the temperature under 5° C. The resulting solution was stirred for 1 hr, after which water (100 mL) and methylene chloride (100 mL) were added. The mixture was separated, and the organic layer was washed twice with 100 mL water, three times with 100 mL of saturated sodium bicarbonate, and once more with 100 mL of water to neutralize the mixture. The organic layer was then separated and dried, filtered and the solvent was removed from the filtrate under reduced pressure to give an oil. The oil was dried under vacuum overnight, to give crude 4-(3-acetoxypropyl)-3,5-dimethyl)-2-formylpyrrole, the compound of formula (7) as a solid.

Workup

  1. customThe reaction flask was evacuated until the solvent
  2. customThe reaction flask was again evacuated until the solvent
  3. filtrationThe resulting suspension was filtered
  4. customto remove the palladium/carbon, and THF
  5. additionwas added
  6. dissolutionto redissolve the solids
  7. customMost of the THF was evaporated off
  8. additionafter which hexanes were added dropwise
  9. stirringwith stirring, to the solution
  10. customto precipitate out
  11. filtrationThe solids were filtered
  12. washrinsed with hexanes
  13. customdried overnight under vacuum

Sources & evidence

ORD record
ord-9b76b56e21fe41829e8c06bf9889c377
Source dataset
uspto-grants-2006_09
Patent number
US07112671B2

Reaction notes

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