3-Quinuclidinol, (-)- → HCID 86641068, compound

HRID 383948Notes

Reaction equation

HRID 383948 reaction equation
[C:1]1([C:7]2[S:11][C:10]3[CH2:12][CH2:13][CH2:14][C:9]=3[C:8]=2[NH2:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:16]12[CH2:23][CH2:22][CH:19]([CH2:20][CH2:21]1)[C@@H:18]([OH:24])[CH2:17]2.Cl.[C:26](Cl)(=O)[O:27]C(CCCCC)CC.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[C:50]([OH:57])(=[O:56])/[CH:51]=[CH:52]/[C:53]([OH:55])=[O:54]>N1C=CC=CC=1.CCO.O>[C:50]([OH:57])(=[O:56])/[CH:51]=[CH:52]/[C:53]([OH:55])=[O:54].[C:1]1([C:7]2[S:11][C:10]3[CH2:12][CH2:13][CH2:14][C:9]=3[C:8]=2[NH:15][C:26](=[O:27])[O:24][C@@H:18]2[CH:19]3[CH2:22][CH2:23][N:16]([CH2:21][CH2:20]3)[CH2:17]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 5

HCID 914043-Quinuclidinol, (-)-HCID 94429TriphosgeneHCID 444972Fumaric AcidHCID 17846645HCID 17846645, compoundHCID 592913755,6-Dihydro-2-phenyl-4H-cyclopenta[b]thiophen-3-amine

Product 1

HCID 86641068HCID 86641068, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1049PyridineSolvent

Procedure

To a solution of 2-phenyl-5,6-dihydro-4H-cyclopenta[b]thiophene-3-amine (110 mg) in pyridine (2 mL) was added (3R)-quinuclidin-3-ol and (3R)-1-azabicyclo[2.2.2]octa-3-yl chlorocarbonate hydrochloride (231 mg) synthesized from triphosgene, followed by stirring at room temperature for 30 minutes, and then stirring at 80° C. for 15 hours. To the reaction mixture was added water, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, then dried over MgSO4, and concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH) to obtain a colorless oily substance (135 mg). This was dissolved in EtOH, and fumaric acid (38 mg) was added thereto. The crystal precipitated was collected by filtration to obtain (3R)-1-azabicyclo[2.2.2]oct-3-yl (2-phenyl-5,6-dihydro-4H-cyclopenta[b]thien-3-yl)carbamate fumarate (103 mg) as a white solid.

Workup

  1. stirringstirring at 80° C. for 15 hours
  2. extractionfollowed by extraction with EtOAc
  3. washThe organic layer was washed with water and brine in this order
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH)
  7. customto obtain a colorless oily substance (135 mg)
  8. customThe crystal precipitated
  9. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-6c73e6f65f4b47f9b76459bcb39a7884
Source dataset
uspto-grants-2013_02
Patent number
US08367696B2

Reaction notes

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