Cyclopropylamine → HCID 66705180, compound

HRID 859899Notes

Reaction equation

HRID 859899 reaction equation
[C:1]1([C@H:7]([N:9]2[CH2:16][C@@H:15]3[C@@H:11]([CH2:12][O:13][C:14]3=[O:17])[CH2:10]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:18]1([NH2:21])[CH2:20][CH2:19]1>C(O)C>[CH:18]1([NH:21][C:14]([C@@H:15]2[C@H:11]([CH2:12][OH:13])[CH2:10][N:9]([C@H:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH3:8])[CH2:16]2)=[O:17])[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 69828CyclopropylamineHCID 66705207HCID 66705207, compound

Product 1

HCID 66705180HCID 66705180, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

(1S,5R)-7-[(1R)-1-Phenylethyl]-3-oxa-7-azabicyclo[3.3.0]octane-2-one (7.73 g, 33.4 mmol) was dissolved in ethanol (92 mL). To this solution, cyclopropylamine (46.3 ml) was added, and the mixture was stirred at 80° C. for 44 hours and was subsequently concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (300 mL) and the solution was washed with water (2×50 mL), followed by drying over anhydrous sodium sulfate and concentration under reduced pressure. To the resulting residue, diisopropyl ether (300 mL) was added and the mixture was heated to form crystal and was then concentrated to approximately ½. The formed crystal was collected by filtration and the collected crystal was washed with diisopropyl ether and was dried under reduced pressure to give 4.41 g of (3R,4S)-N-cyclopropyl-4-hydroxymethyl-1-[(1S)-1-phenylethyl]pyrrolidine-3-carboxamide as a white crystal. The filtrate and the washing solution were combined and the combined solvent was concentrated under reduced pressure. The resulting residue was purified on a silica gel column (eluant=hexane:ethyl acetate=1:1, shifted to ethyl acetate) to obtain additional 1.50 g of (3R,4S)-N-cyclopropyl-4-hydroxymethyl-1-[(1S)-1-phenylethyl]pyrrolidine-3-carboxamide. The total amount of the compound was 5.91 g.

Workup

  1. concentrationwas subsequently concentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in ethyl acetate (300 mL)
  3. washthe solution was washed with water (2×50 mL)
  4. dry with materialby drying over anhydrous sodium sulfate and concentration under reduced pressure
  5. additionTo the resulting residue, diisopropyl ether (300 mL) was added
  6. temperaturethe mixture was heated
  7. customto form crystal
  8. concentrationwas then concentrated to approximately ½
  9. filtrationThe formed crystal was collected by filtration
  10. washthe collected crystal was washed with diisopropyl ether
  11. customwas dried under reduced pressure

Sources & evidence

ORD record
ord-3a3b4a4530ad4179ac1d7d092a76b58a
Source dataset
uspto-grants-2006_12
Patent number
US07153851B2

Reaction notes

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