Pyrrolidine → Methyl 2-[3-(tert-butoxycarbonylamino)propoxy]-4-(pyrrolidin-1-yl)benzoate

HRID 644237Notes

Reaction equation

HRID 644237 reaction equation
F[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH2:13][CH2:14][CH2:15][NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:3]=1.[NH:24]1[CH2:28][CH2:27][CH2:26][CH2:25]1>>[C:20]([O:19][C:17]([NH:16][CH2:15][CH2:14][CH2:13][O:12][C:4]1[CH:3]=[C:2]([N:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7])=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

3

Reactant 2

HCID 31268PyrrolidineHCID 57602453Methyl 4-fluoro-2-(3-tert-butoxycarbonylaminopropoxy)benzoate

Product 1

HCID 68532729Methyl 2-[3-(tert-butoxycarbonylamino)propoxy]-4-(pyrrolidin-1-yl)benzoateYield 99%

Conditions

Temperature
80 °C

Procedure

A mixture of methyl 4-fluoro-2-[3-(tert-butoxycarbonylamino)propoxy]benzoate (8.148 g, 25 mmol) and pyrrolidine (20.87 mL, 250 mmol) was purged with nitrogen and heated to 80° C. for 3 hours. The reaction was concentrated in vacuo. After diluting with EtOAc, the mixture was cooled to 0° C., acidified with satd citric acid, and extracted with EtOAc. The organic layer was washed with satd citric acid and water, dried (Na2 SO4), and concentrated. The resulting residue was absorbed onto silica gel and chromatographed (20% EtOAc/hexane to 35% EtOAc/hexane). The resulting product was triturated with Et2O/hexane to give the desired product as a white solid (9.05 g, 99%).

Workup

  1. customwas purged with nitrogen
  2. concentrationThe reaction was concentrated in vacuo
  3. additionAfter diluting with EtOAc
  4. temperaturethe mixture was cooled to 0° C.
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with satd citric acid and water
  7. customdried (Na2 SO4)
  8. concentrationconcentrated
  9. customThe resulting residue was absorbed onto silica gel
  10. customchromatographed (20% EtOAc/hexane to 35% EtOAc/hexane)
  11. customThe resulting product was triturated with Et2O/hexane

Sources & evidence

ORD record
ord-ef9c25c0b7a94ae39521a612818ad341
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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