Water → 5,6-Dihydro-2-phenyl-4H-cyclopenta[b]thiophen-3-amine

HRID 383913Notes

Reaction equation

HRID 383913 reaction equation
[C:1]1([C:7]2[S:11][C:10]3[CH2:12][CH2:13][CH2:14][C:9]=3[C:8]=2C(O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=CC(P([N:32]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.O>C1(C)C=CC=CC=1.CN(C=O)C>[C:1]1([C:7]2[S:11][C:10]3[CH2:12][CH2:13][CH2:14][C:9]=3[C:8]=2[NH2:32])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 962WaterHCID 199401P,P-Diphenylphosphinic azideHCID 59291346HCID 59291346, compound

Product 1

HCID 592913755,6-Dihydro-2-phenyl-4H-cyclopenta[b]thiophen-3-amine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-phenyl-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid and TEA in toluene was added a solution of DPPA in toluene, followed by stirring at room temperature for 40 minutes, and then stirring at 90° C. for 60 minutes. Furthermore, a solution of (3R)-quinuclidinole in DMF was added thereto, followed by heating under reflux for 15 hours. To the reaction liquid was added water, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried over MgSO4, and then concentrated under reduced pressure. The oily substance obtained was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane:EtOAc) to obtain 2-phenyl-5,6-dihydro-4H-cyclopenta[b]thiophene-3-amine as a pale brown oil, but not a desired (3R)-1-azabicyclo[2.2.2]oct-3-yl(2-phenyl-5,6-dihydro-4H-cyclopenta[b]thien-3-yl)carbamate.

Workup

  1. stirringstirring at 90° C. for 60 minutes
  2. temperatureby heating
  3. temperatureunder reflux for 15 hours
  4. customTo the reaction liquid
  5. extractionfollowed by extraction with EtOAc
  6. washThe organic layer was washed with water and brine in this order
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe oily substance obtained
  10. customwas purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, hexane:EtOAc)

Sources & evidence

ORD record
ord-b7991e372bb94dcc8812754e169cc886
Source dataset
uspto-grants-2013_02
Patent number
US08367696B2

Reaction notes

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