Water → Methyl 3-formyl-4,5-dimethyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrole-2-carboxylate

HRID 433878Notes

Reaction equation

HRID 433878 reaction equation
CC(C)([O-])C.[K+].[CH:7]([C:9]1[C:13]([CH3:14])=[C:12]([CH3:15])[NH:11][C:10]=1[C:16]([O:18][CH3:19])=[O:17])=[O:8].[CH3:20][C@H:21]1[CH2:23][C@@H:22]1[CH2:24]Br.O>O1CCCC1.C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].C[C@H]1C[C@@H]1CBr>[CH:7]([C:9]1[C:13]([CH3:14])=[C:12]([CH3:15])[N:11]([CH2:20][C@H:21]2[CH2:23][C@@H:22]2[CH3:24])[C:10]=1[C:16]([O:18][CH3:19])=[O:17])=[O:8]

Participants

9

Reactant 4

HCID 962WaterHCID 10773740Methyl 3-formyl-4,5-dimethyl-1H-pyrrole-2-carboxylateHCID 12110454(1S,2S)-1-(bromomethyl)-2-methylcyclopropaneHCID 23665647Potassium tert-butoxide

Product 1

HCID 12110455Methyl 3-formyl-4,5-dimethyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrole-2-carboxylateYield 103.9%

Reagents, catalysts & solvents 4

HCID 2855718-Crown-6CatalystHCID 12110454(1S,2S)-1-(bromomethyl)-2-methylcyclopropaneCatalystHCID 23665647Potassium tert-butoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Potassium tert-butoxide (3.94 g, 35.1 mmol) was added to a solution of methyl 3-formyl-4,5-dimethylpyrrole-2-carboxylate (5.79 g, 31.9 mmol) and 18-crown-6 (0.41 g, 1.55 mmol) in tetrahydrofuran (130 ml) and the mixture was stirred at room temperature for 1 hour. After dropwise addition over 30 minutes of (1S,2S)-2-methylcyclopropylmethyl bromide (5.71 g, 38.3 mmol) to the reaction mixture at 50° C., the mixture was heated under reflux for 3 hours. Potassium tert-butoxide (0.36 g, 3.22 mmol) and (1S,2S)-2-methylcyclopropylmethyl bromide (0.48 g, 3.21 mmol) was further added to the mixture and this mixture was heated for 1 hour. The reaction mixture was poured into iced water and extracted with ethyl acetate. The extract was washed with water and saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to afford the desired compound (8.26 g, 100%) as a pale brown oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 hours
  3. temperaturethis mixture was heated for 1 hour
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with water and saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-0dc97801e5514eb9a8955208a882fd3e
Source dataset
uspto-grants-2003_12
Patent number
US06670360B2

Reaction notes

Loading…