4-(R)-[1-[N-(tert-butoxycarbonyl)-N-(ethyl)Amino]Cyclopropyl]-1-[1-(S)-phenylethyl]Pyrrolidin-2-one → 3-(R)-[1-[N-(tert-butoxycarbonyl)-N-(ethyl)Amino]Cyclopropyl]-1-[1-(S)-phenylethyl]Pyrrolidine

HRID 600902Notes

Reaction equation

HRID 600902 reaction equation
[C:1]([O:5][C:6]([N:8]([C:11]1([C@H:14]2[CH2:18][N:17]([C@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH3:20])[C:16](=O)[CH2:15]2)[CH2:13][CH2:12]1)[CH2:9][CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]>O1CCCC1>[C:1]([O:5][C:6]([N:8]([C:11]1([C@@H:14]2[CH2:15][CH2:16][N:17]([C@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH3:20])[CH2:18]2)[CH2:12][CH2:13]1)[CH2:9][CH3:10])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

3

Reactant 1

HCID 672718654-(R)-[1-[N-(tert-butoxycarbonyl)-N-(ethyl)Amino]Cyclopropyl]-1-[1-(S)-phenylethyl]Pyrrolidin-2-one

Product 1

HCID 672719343-(R)-[1-[N-(tert-butoxycarbonyl)-N-(ethyl)Amino]Cyclopropyl]-1-[1-(S)-phenylethyl]PyrrolidineYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-(R)-[1-[N-(tert-butoxycarbonyl)-N-(ethyl)amino]cyclopropyl]-1-[1-(S)-phenylethyl]pyrrolidin-2-one (4.56 g, 12.1 mmol) was dissolved in anhydrous tetrahydrofuran (80 ml), and a 1.0M borane-tetrahydrofuran complex/tetrahydrofuran solution (48.0 ml, 48.0 mmol) was added dropwise in while stirring and cooling with ice. After completion of dripping, the reaction solution was stirred for 16 hours under the condition of from ice cooling to room temperature. After concentrating the reaction solution under a reduced pressure, a 9:1 mixed solution (100 ml) of ethanol and water was added thereto, and after adding triethylamine (5 ml), it was heated under reflux for 4 hours. After cooling the reaction solution to room temperature, concentration was performed under a reduced pressure, saturated sodium bicarbonate water (100 ml) was added to the residue, extraction with chloroform (100 ml×2) was performed, and then the combined organic layer was washed with saturated saline solution (100 ml) and then dried over anhydrous sodium sulfate. After filtering, the filtrate was concentrated under a reduced pressure, the concentrate was applied to a silica gel chromatography, and 4.26 g (99%) of the title compound was obtained in the form of a colorless syrup from a chloroform:methanol=100:1 to 95:5 eluate.

Workup

  1. temperaturecooling with ice
  2. stirringthe reaction solution was stirred for 16 hours under the condition of from ice cooling to room temperature
  3. concentrationAfter concentrating the reaction solution under a reduced pressure
  4. additiona 9:1 mixed solution (100 ml) of ethanol and water was added
  5. additionafter adding triethylamine (5 ml), it
  6. temperaturewas heated
  7. temperatureunder reflux for 4 hours
  8. concentrationconcentration
  9. additionwas added to the residue, extraction with chloroform (100 ml×2)
  10. washthe combined organic layer was washed with saturated saline solution (100 ml)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationAfter filtering
  13. concentrationthe filtrate was concentrated under a reduced pressure

Sources & evidence

ORD record
ord-4edc7fde3e3a4edd834f5627a1e0302a
Source dataset
uspto-grants-2011_03
Patent number
US07902226B2

Reaction notes

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