Nitrogen → 2-Benzylhexahydrocyclopenta[c]pyrrol-4(1H)-one

HRID 253180Notes

Reaction equation

HRID 253180 reaction equation
N#N.[C:3]1(=[O:8])[CH2:7][CH2:6][CH:5]=[CH:4]1.[CH2:9]([N:16]([CH2:22]OC)[CH2:17][Si](C)(C)C)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O>C(Cl)Cl.COC(C)(C)C.FC(F)(F)C(O)=O>[CH2:9]([N:16]1[CH2:22][CH:4]2[C:3](=[O:8])[CH2:7][CH2:6][CH:5]2[CH2:17]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 962WaterHCID 135882-Cyclopenten-1-oneHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine2×

Product 1

HCID 134637692-Benzylhexahydrocyclopenta[c]pyrrol-4(1H)-oneYield 774.1%

Reagents, catalysts & solvents 3

HCID 6422Trifluoroacetic acidCatalystHCID 6344DichloromethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A 3-neck, 1-L round bottom flask equipped with an addition funnel, internal thermometer, and N2 inlet at RT was charged with cyclopentenone (16.48 g, 0.20 mol) in 0.5 L of CH2Cl2. Benzyl(methoxymethyl)trimethylsilylmethylamine (5.0 grams, 21 mmol) and trifluoroacetic acid (TFA) (1.07 mL, 13.9 mmol) were added. To this mixture was added additional benzyl(methoxymethyl)-trimethylsilylmethylamine (40 g, 0.168 mol) dropwise via addition funnel over 1 hour with the reaction temperature being maintained below 25° C. (water bath). After the addition was complete, the mixture was stirred for 4 h. The mixture was washed with 1×100 mL 10% Na2CO3. The layers were separated and the organic layer was washed with 1×100 mL 23% NaCl. The organic extract was concentrated under reduced pressure to give an oil. The oil was redissolved in methyl-t-butyl ether (250 mL) and extracted into 1M H3PO4 (200 mL). The aqueous layer was basified with 50% NaOH to pH 12. The product was extracted with methyl-t-butyl ether (250 mL). The layers were separated and the organic layer was washed with 23% NaCl. The layers were separated. The organic layer was charged with acetonitrile (50 mL) and silica gel (10 gms). The mixture was stirred 5 minutes and filtered through a silica gel pad (10 grams). The filtrate was concentrated to give the title compound (35.0 grams, 81.4% of theory), which was carried on to the next step without further purification. MS (ESI/APCI) m/z 216 (M+H)+.

Workup

  1. additiondropwise via addition funnel over 1 hour with the reaction temperature
  2. additionAfter the addition
  3. washThe mixture was washed with 1×100 mL 10% Na2CO3
  4. customThe layers were separated
  5. washthe organic layer was washed with 1×100 mL 23% NaCl
  6. extractionThe organic extract
  7. concentrationwas concentrated under reduced pressure
  8. customto give an oil
  9. extractionextracted into 1M H3PO4 (200 mL)
  10. extractionThe product was extracted with methyl-t-butyl ether (250 mL)
  11. customThe layers were separated
  12. washthe organic layer was washed with 23% NaCl
  13. customThe layers were separated
  14. additionThe organic layer was charged with acetonitrile (50 mL) and silica gel (10 gms)
  15. stirringThe mixture was stirred 5 minutes
  16. filtrationfiltered through a silica gel pad (10 grams)
  17. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-515797e220ef4dd4a34951b0bcbf0bed
Source dataset
uspto-grants-2011_01
Patent number
US07872010B2

Reaction notes

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