4-(R)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(S)-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone → 4-(R)-(1-tert-Butoxycarbonylaminocyclopropyl)-3-(S)-fluoro-1-[1-(S)-phenylethyl]pyrrolidine

HRID 635112Notes

Reaction equation

HRID 635112 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([C@H:12]2[CH2:16][N:15]([C@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[C:14](=O)[C@H:13]2[F:26])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>O1CCCC1>[C:1]([O:5][C:6]([NH:8][C:9]1([C@H:12]2[CH2:16][N:15]([C@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[CH2:14][C@H:13]2[F:26])[CH2:10][CH2:11]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

3

Reactant 1

HCID 111005394-(R)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(S)-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone

Product 1

HCID 112449864-(R)-(1-tert-Butoxycarbonylaminocyclopropyl)-3-(S)-fluoro-1-[1-(S)-phenylethyl]pyrrolidineYield 99.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under a nitrogen atmosphere, a 1 M solution of borane-tetrahydrofuran complex in tetrahydrofuran (120 ml) was added dropwise under ice cooling into a solution of 4-(R)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(S)-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone in tetrahydrofuran (120 ml) and the mixture was stirred at room temperature for 5 hours. After evaporating the solvent under reduced pressure, a solvent mixture (200 ml) of ethanol with water (4:1) and triethylamine (20 ml) were added to the residue followed by heating under reflux for 2 hours. Then, the liquid reaction mixture was concentrated under reduced pressure and chloroform (400 ml) was added to the residue. After washing with a saturated aqueous solution of sodium chloride, the organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was subjected to flash silica gel column chromatography (eluent: n-hexane:ethyl acetate=1:2) to obtain 7.84 g (99.4%) of the title compound as a colorless oily substance.

Workup

  1. customAfter evaporating the solvent under reduced pressure
  2. additiona solvent mixture (200 ml) of ethanol with water (4:1) and triethylamine (20 ml) were added to the residue
  3. temperatureby heating
  4. temperatureunder reflux for 2 hours
  5. customThen, the liquid reaction mixture
  6. concentrationwas concentrated under reduced pressure and chloroform (400 ml)
  7. additionwas added to the residue
  8. washAfter washing with a saturated aqueous solution of sodium chloride
  9. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-68d3140b1d2e47319313be7f6b510f29
Source dataset
uspto-grants-2001_02
Patent number
US06184388B2

Reaction notes

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