Hydrochloric Acid → 1-allyl 3-tert-butyl (2S)-2-[(methoxy)methyl]-2,5-dihydro-1H-pyrrole-1,3-dicarboxylate

HRID 1374433Notes

Reaction equation

HRID 1374433 reaction equation
O[CH:2]1[CH2:6][N:5]([C:7]([O:9][CH2:10][CH:11]=[CH2:12])=[O:8])[C@H:4]([CH2:13][O:14][CH2:15]OC)[CH:3]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].CS(Cl)(=O)=O.C(N(CC)CC)C.Cl.C1CCN2C(=NCCC2)CC1>ClCCl.CN(C)C1C=CN=CC=1>[CH3:15][O:14][CH2:13][C@@H:4]1[C:3]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:2][CH2:6][N:5]1[C:7]([O:9][CH2:10][CH:11]=[CH2:12])=[O:8]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 865925281-allyl 3-tert-butyl (2S)-4-hydroxy-2-[(methoxymethoxy)methyl]-1,3-pyrrolidinedicarboxylate

Product 1

HCID 865925301-allyl 3-tert-butyl (2S)-2-[(methoxy)methyl]-2,5-dihydro-1H-pyrrole-1,3-dicarboxylateYield 72.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-allyl 3-tert-butyl (2S)-4-hydroxy-2-[(methoxymethoxy)methyl]-1,3-pyrrolidinedicarboxylate (1.47 g, 4.26 mmol) in dichloromethane (20 ml) were added at −30° C. methanesulfonyl chloride (0.50 ml, 6.5 mmol), triethylamine (1.2 ml, 8.6 mmol) and 4-dimethylaminopyridine (52 mg, 0.43 mmol) and the mixture was stirred at 0° C. for 75 minutes. The reaction mixture was poured into diluted hydrochloric acid and the mixture was extracted three times with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed in vacuo. The residue was dissolved in dicholomethane (10 ml) and the solution was cooled to 0° C. and thereto was added DBU (0.95 ml, 6.4 mmol). The mixture was raised to room temperature and stirred just for 30 minutes. The reaction mixture was poured into diluted hydrochloric acid and the solution was extracted three times with ethyl acetate. The organic layer was washed with water and then a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed in vacuo. The residue was purified with silica gel (30 g) chromatography (hexane/ethyl acetate=4/1→2/1) to give 1-allyl 3-tert-butyl (2S)-2-[(methoxy)methyl]-2,5-dihydro-1H-pyrrole-1,3-dicarboxylate (0.92 g, 66%).

Workup

  1. extractionthe mixture was extracted three times with chloroform
  2. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed in vacuo
  5. dissolutionThe residue was dissolved in dicholomethane (10 ml)
  6. temperaturethe solution was cooled to 0° C.
  7. temperatureThe mixture was raised to room temperature
  8. stirringstirred just for 30 minutes
  9. extractionthe solution was extracted three times with ethyl acetate
  10. washThe organic layer was washed with water
  11. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate
  12. customThe solvent was removed in vacuo
  13. customThe residue was purified with silica gel (30 g) chromatography (hexane/ethyl acetate=4/1→2/1)

Sources & evidence

ORD record
ord-fb52af5dd6064752b20aa754bc81674c
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

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