Acetone → 5-((E)-(3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene)methyl)-1-((7R,8aR)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-1H-benzo[d]imidazol-2(3H)-one. tosylate salt

HRID 244355Notes

Reaction equation

HRID 244355 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:36]=1)[O:7][CH2:8][C:9]1[CH:35]=[CH:34][CH:33]=[CH:32][C:10]=1/[C:11]/2=[CH:12]\[C:13]1[CH:31]=[CH:30][C:16]2[N:17]([C@H:21]3[CH2:29][N:28]4[C@@H:23]([CH2:24][O:25][CH2:26][CH2:27]4)[CH2:22]3)[C:18](=[O:20])[NH:19][C:15]=2[CH:14]=1.O.[C:38]1([CH3:48])[CH:43]=[CH:42][C:41]([S:44]([OH:47])(=[O:46])=[O:45])=[CH:40][CH:39]=1.CC(C)=O.C(#N)C>CC(N(C)C)=O.C1COCC1>[S:44]([C:41]1[CH:42]=[CH:43][C:38]([CH3:48])=[CH:39][CH:40]=1)([OH:47])(=[O:46])=[O:45].[F:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:36]=1)[O:7][CH2:8][C:9]1[CH:35]=[CH:34][CH:33]=[CH:32][C:10]=1/[C:11]/2=[CH:12]\[C:13]1[CH:31]=[CH:30][C:16]2[N:17]([C@H:21]3[CH2:29][N:28]4[C@@H:23]([CH2:24][O:25][CH2:26][CH2:27]4)[CH2:22]3)[C:18](=[O:20])[NH:19][C:15]=2[CH:14]=1

Participants

7

Reactant 4

HCID 180AcetoneHCID 6342AcetonitrileHCID 521998p-Toluenesulfonic acid monohydrateHCID 468941193-[(7R,8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl]-6-[(E)-(3-fluoro-6H-benzo[c][1]benzoxepin-11-ylidene)methyl]-1H-benzimidazol-2-one

Product 1

HCID 899760645-((E)-(3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene)methyl)-1-((7R,8aR)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-1H-benzo[d]imidazol-2(3H)-one. tosylate salt

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

Dissolve 98.0 mg of 5-((E)-(3-fluorodibenzo[b,e]oxepin-11(6H)-ylidene)methyl)-1-((7R,8aR)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-7-yl)-1H-benzo[d]imidazol-2(3H)-one (prepared essentially as described in Example 1) in 2.5 mL of DMAC. Add 1.2 eq. of p-toluenesulfonic acid monohydrate and stir until solution is clear and colorless. Add 2 mL of 88% acetone then 16 mL of water then evaporate to remove solvents. To the resulting clear oil, add 1 mL of acetone and sonicate. Dry the resulting gel to obtain an off-white solid. Dissolve the solid again in 1:10 THF:H2O and evaporate to obtain a clear oil then sonicate with 5 mL of acetonitrile. After a white solid precipitates, slurry the sample overnight. Filter and dry to obtain a solid.

Workup

  1. customprepared essentially
  2. custom16 mL of water then evaporate
  3. customto remove solvents
  4. additionTo the resulting clear oil, add 1 mL of acetone
  5. customsonicate
  6. customDry the resulting gel
  7. customto obtain an off-white solid
  8. customH2O and evaporate
  9. customto obtain a clear oil
  10. customAfter a white solid precipitates
  11. customthe sample overnight
  12. filtrationFilter
  13. customdry
  14. customto obtain a solid

Sources & evidence

ORD record
ord-1b44252e28a848a390060de466af983b
Source dataset
uspto-grants-2014_02
Patent number
US08658638B2

Reaction notes

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