p-Toluenesulfonic acid monohydrate → N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-(3-chlorophenyl)-1,3-oxazole-2-carboxamide 4-methylbenzenesulfonate

HRID 2298370Notes

Reaction equation

HRID 2298370 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:12][C:11]([C:13]([O:15]CC)=O)=[N:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:18][C@@H:19]1[CH:24]2[CH2:25][CH2:26][N:21]([CH2:22][CH2:23]2)[CH2:20]1.O.[C:28]1([CH3:38])[CH:33]=[CH:32][C:31]([S:34]([OH:37])(=[O:36])=[O:35])=[CH:30][CH:29]=1>CCO>[CH3:38][C:28]1[CH:29]=[CH:30][C:31]([S:34]([OH:37])(=[O:36])=[O:35])=[CH:32][CH:33]=1.[N:21]12[CH2:26][CH2:25][CH:24]([CH2:23][CH2:22]1)[C@@H:19]([NH:18][C:13]([C:11]1[O:12][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)=[CH:9][N:10]=1)=[O:15])[CH2:20]2

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 719215(3R)-1-Azabicyclo(2.2.2)octan-3-amineHCID 22350710Ethyl 5-(3-chlorophenyl)oxazole-2-carboxylate

Product 1

HCID 86584883N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-(3-chlorophenyl)-1,3-oxazole-2-carboxamide 4-methylbenzenesulfonateYield 70.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of the product from Step 79c (0.419 g, 1.66 mmol, 1.0 eq), (R)-(+)-3-aminoquinuclidine (0.221 g, 1.75 mmol, 1.05 eq) and EtOH (4.0 mL) is heated under reflux. After 64 h, the mixture is cooled and the contents are filtered through glass wool into p-toluenesulfonic acid monohydrate (0.315 g, 1.65 mmol, 1.0 eq). The resulting solid is filtered and dried in vacuity to afford the title compound (0.59 g, 65%). HRMS (FAB) calculated for C17H18ClN3O2+H1 332.1165, found 332.1180.

Workup

  1. temperatureis heated
  2. temperatureunder reflux
  3. temperaturethe mixture is cooled
  4. filtrationThe resulting solid is filtered
  5. customdried in vacuity

Sources & evidence

ORD record
ord-850d867653b34a6798c6a743fcabbdb5
Source dataset
uspto-grants-2002_12
Patent number
US06492385B2

Reaction notes

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